rs35400405
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_001114753.3(ENG):c.14C>T(p.Thr5Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,593,366 control chromosomes in the GnomAD database, including 753 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T5T) has been classified as Benign.
Frequency
Consequence
NM_001114753.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.14C>T | p.Thr5Met | missense_variant | 1/15 | ENST00000373203.9 | |
ENG | NM_000118.4 | c.14C>T | p.Thr5Met | missense_variant | 1/14 | ||
ENG | NM_001406715.1 | c.14C>T | p.Thr5Met | missense_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.14C>T | p.Thr5Met | missense_variant | 1/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.14C>T | p.Thr5Met | missense_variant | 1/14 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0434 AC: 6610AN: 152188Hom.: 259 Cov.: 32
GnomAD3 exomes AF: 0.0215 AC: 4471AN: 207920Hom.: 97 AF XY: 0.0192 AC XY: 2166AN XY: 112672
GnomAD4 exome AF: 0.0204 AC: 29394AN: 1441060Hom.: 494 Cov.: 31 AF XY: 0.0197 AC XY: 14060AN XY: 715048
GnomAD4 genome ? AF: 0.0435 AC: 6621AN: 152306Hom.: 259 Cov.: 32 AF XY: 0.0410 AC XY: 3057AN XY: 74482
ClinVar
Submissions by phenotype
not specified Benign:7
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 22, 2014 | Thr5Met in exon 1 of ENG: This variant is not expected to have clinical signific ance because it has been identified in 10% (445/4390) of African American chromo somes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs35400405). - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 11, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 18, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Telangiectasia, hereditary hemorrhagic, type 1 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Hereditary hemorrhagic telangiectasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at