rs587776357
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001145809.2(MYH14):c.3468-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,611,082 control chromosomes in the GnomAD database, including 503 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001145809.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.3468-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000642316.2 | NP_001139281.1 | |||
MYH14 | NM_001077186.2 | c.3369-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_001070654.1 | ||||
MYH14 | NM_024729.4 | c.3345-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_079005.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.3468-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001145809.2 | ENSP00000493594 |
Frequencies
GnomAD3 genomes AF: 0.0171 AC: 2605AN: 152200Hom.: 42 Cov.: 33
GnomAD3 exomes AF: 0.0177 AC: 4276AN: 242056Hom.: 59 AF XY: 0.0181 AC XY: 2398AN XY: 132318
GnomAD4 exome AF: 0.0231 AC: 33626AN: 1458764Hom.: 461 Cov.: 31 AF XY: 0.0226 AC XY: 16368AN XY: 725514
GnomAD4 genome AF: 0.0171 AC: 2604AN: 152318Hom.: 42 Cov.: 33 AF XY: 0.0154 AC XY: 1150AN XY: 74482
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 2017 | 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, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 09, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 3468-3C>T in Intron 27 of MYH14: This variant is not expected to have clinical s ignificance because it has been identified in 2.5% (165/6628) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs78192108). - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 13, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Autosomal dominant nonsyndromic hearing loss 4A Benign:1Other:1
not provided, no classification provided | literature only | Genomic Research Center, Shahid Beheshti University of Medical Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at