NM_001134665.3(TRMT10A):c.151C>T (p.Gln51Ter) AND Microcephaly, short stature, and impaired glucose metabolism 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 21, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004789668.1

Allele description [Variation Report for NM_001134665.3(TRMT10A):c.151C>T (p.Gln51Ter)]

NM_001134665.3(TRMT10A):c.151C>T (p.Gln51Ter)

Gene:

TRMT10A:tRNA methyltransferase 10A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q23

Genomic location:

Preferred name:

NM_001134665.3(TRMT10A):c.151C>T (p.Gln51Ter)

HGVS:

NC_000004.12:g.99559188G>A
NG_011469.1:g.106G>A
NG_041774.1:g.9870C>T
NM_001134665.3:c.151C>TMANE SELECT
NM_001134666.3:c.151C>T
NM_001375880.1:c.151C>T
NM_001375881.1:c.151C>T
NM_001375882.1:c.151C>T
NM_152292.5:c.151C>T
NP_001128137.1:p.Gln51Ter
NP_001128138.1:p.Gln51Ter
NP_001362809.1:p.Gln51Ter
NP_001362810.1:p.Gln51Ter
NP_001362811.1:p.Gln51Ter
NP_689505.1:p.Gln51Ter
NC_000004.11:g.100480345G>A
NM_001134665.2:c.151C>T

Protein change:

Q51*

Molecular consequence:

NM_001134665.3:c.151C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001134666.3:c.151C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001375880.1:c.151C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001375881.1:c.151C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001375882.1:c.151C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_152292.5:c.151C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Microcephaly, short stature, and impaired glucose metabolism 1 (MSSGM1)
Identifiers:: MONDO: MONDO:0000208; MedGen: C4014997; Orphanet: 391408; OMIM: 616033

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005399760	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 21, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26535115, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005399760

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 21, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities.

Narayanan M, Ramsey K, Grebe T, Schrauwen I, Szelinger S, Huentelman M, Craig D, Narayanan V; C4RCD Research Group.

F1000Res. 2015;4:912. doi: 10.12688/f1000research.7106.1.

PubMed [citation]

PMID:: 26535115
PMCID:: PMC4617320

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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005399760.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with microcephaly, short stature, and impaired glucose metabolism 1 (MIM#616033). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0702 - Other NMD predicted variants comparable to the one identified in this case have strong previous evidence for pathogenicity (DECIPHER, PMID:26535115). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) by trio analysis. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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

Last Updated: Nov 30, 2024

ClinVar

Relating variation to medicine