NM_004568.6(SERPINB6):c.314C>A (p.Ser105Tyr) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Mar 22, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001547089.25

Allele description [Variation Report for NM_004568.6(SERPINB6):c.314C>A (p.Ser105Tyr)]

NM_004568.6(SERPINB6):c.314C>A (p.Ser105Tyr)

Gene:

SERPINB6:serpin family B member 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p25.2

Genomic location:

Preferred name:

NM_004568.6(SERPINB6):c.314C>A (p.Ser105Tyr)

HGVS:

NC_000006.12:g.2954708G>T
NG_027692.1:g.22458C>A
NM_001195291.3:c.326C>A
NM_001271822.2:c.356C>A
NM_001271823.2:c.371C>A
NM_001271824.2:c.314C>A
NM_001271825.2:c.314C>A
NM_001297699.2:c.314C>A
NM_001297700.2:c.314C>A
NM_001374515.1:c.326C>A
NM_001374516.1:c.314C>A
NM_001374517.1:c.182C>A
NM_004568.6:c.314C>AMANE SELECT
NP_001182220.2:p.Ser109Tyr
NP_001258751.1:p.Ser119Tyr
NP_001258752.1:p.Ser124Tyr
NP_001258753.1:p.Ser105Tyr
NP_001258754.1:p.Ser105Tyr
NP_001284628.1:p.Ser105Tyr
NP_001284629.1:p.Ser105Tyr
NP_001361444.1:p.Ser109Tyr
NP_001361445.1:p.Ser105Tyr
NP_001361446.1:p.Ser61Tyr
NP_004559.4:p.Ser105Tyr
NP_004559.4:p.Ser105Tyr
NC_000006.11:g.2954942G>T
NM_001195291.1:c.314C>A
NM_004568.5:c.314C>A
NR_164657.1:n.359C>A
p.Ser105Tyr

Protein change:

S105Y

Links:

dbSNP: rs148530934

NCBI 1000 Genomes Browser:

rs148530934

Molecular consequence:

NM_001195291.3:c.326C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271822.2:c.356C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271823.2:c.371C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271824.2:c.314C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271825.2:c.314C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001297699.2:c.314C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001297700.2:c.314C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374515.1:c.326C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374516.1:c.314C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374517.1:c.182C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004568.6:c.314C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164657.1:n.359C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001766714	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Aug 25, 2020)	germline	clinical testing	Citation Link,
SCV002182846	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002497378	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Feb 1, 2022)	germline	clinical testing	Citation Link,
SCV004227180	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV001766714.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002182846.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 105 of the SERPINB6 protein (p.Ser105Tyr). This variant is present in population databases (rs148530934, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SERPINB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 229240). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV002497378.18

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV004227180.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

BS1_supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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