VCV003358858.1 - ClinVar

NM_017436.7(A4GALT):c.218del (p.Gly73fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Affects

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_017436.7(A4GALT):c.218del (p.Gly73fs)

Variation ID: 3358858 Accession: VCV003358858.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 22q13.2 22: 42693734 (GRCh38) [ NCBI UCSC ] 22: 43089740 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 8, 2024	Oct 8, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_017436.7:c.218del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_059132.1:p.Gly73fs	frameshift
NM_001318038.3:c.218del	NP_001304967.1:p.Gly73fs	frameshift
NC_000022.11:g.42693735del
NC_000022.10:g.43089741del
NG_007495.2:g.32568del
LRG_795:g.32568del
LRG_795t1:c.218del	LRG_795p1:p.Gly73fs

... more HGVS ... less HGVS

Protein change

G73fs

Other names

Canonical SPDI

NC_000022.11:42693733:CC:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
A4GALT		-	-	GRCh38 GRCh37	94	139

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Blood group, P1PK system	Affects (1)	no assertion criteria provided	-	RCV004737797.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Affects (-)	no assertion criteria provided Method: research	Blood group, P1PK system Affected status: yes Allele origin: inherited	National Institute of Immunohaematology, Indian Council of Medical Research Accession: SCV005328488.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Publications: DOI: 10.1111/trf.12355 DOI: 10.1111/trf.12355 DOI: 10.1074/jbc.C000625200 DOI: 10.1074/jbc.C000625200 DOI: 10.1111/j.1365-2141.2004.04… DOI: 10.1111/j.1365-2141.2004.04930.x Comment: The NM_017436.7, c.72dupC, is a frameshift insertion in a exon 3 of a A4GALT gene which is predicted to result in a premature termination of … (more) The NM_017436.7, c.72dupC, is a frameshift insertion in a exon 3 of a A4GALT gene which is predicted to result in a premature termination of protein, and likely results in absent or disrupted protein product (A4GALT). This variant resulted in rare p phenotype found in a antenatal women with a history of recurrent miscarriages Individuals with the p phenotype lack the P, P1, and P(k) antigens. The anti-PP1Pk antibody has been naturally produced in p phenotype individual. These antibodies are responsible for severe hemolytic transfusion reactions (HTR) and haemolytic disease of new born (HDFN). This phenotype functionally confirmed by serological assay using preserved anti-PP1Pk antibody. This novel variant is not present in gnomAD and not reported in literature. In summary, this variant meets criteria to be classified as affecting for rare p phenotype based on www.isbtweb.org/resource/p1pkalleles . (less)

Comment:

The NM_017436.7, c.72dupC, is a frameshift insertion in a exon 3 of a A4GALT gene which is predicted to result in a premature termination of protein, and likely results in absent or disrupted protein product (A4GALT). This variant resulted in rare p phenotype found in a antenatal women with a history of recurrent miscarriages Individuals with the p phenotype lack the P, P1, and P(k) antigens. The anti-PP1Pk antibody has been naturally produced in p phenotype individual. These antibodies are responsible for severe hemolytic transfusion reactions (HTR) and haemolytic disease of new born (HDFN). This phenotype functionally confirmed by serological assay using preserved anti-PP1Pk antibody. This novel variant is not present in gnomAD and not reported in literature. In summary, this variant meets criteria to be classified as affecting for rare p phenotype based on www.isbtweb.org/resource/p1pkalleles .

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
-	-	-	-	DOI: 10.1074/jbc.C000625200
-	-	-	-	DOI: 10.1111/j.1365-2141.2004.04930.x
-	-	-	-	DOI: 10.1111/trf.12355

Text-mined citations for this variant ...

Record last updated Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_017436.7(A4GALT):c.218del (p.Gly73fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...