rs142696359
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001145809.2(MYH14):c.1115-4C>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 0.000415 in 1,613,446 control chromosomes in the GnomAD database, including 1 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 Conflicting classifications of pathogenicity (no stars).
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 -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.1115-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000642316.2 | NP_001139281.1 | |||
MYH14 | NM_001077186.2 | c.1115-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_001070654.1 | ||||
MYH14 | NM_024729.4 | c.1091-4C>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.1115-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001145809.2 | ENSP00000493594 |
Frequencies
GnomAD3 genomes AF: 0.000361 AC: 55AN: 152156Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000459 AC: 114AN: 248602Hom.: 2 AF XY: 0.000437 AC XY: 59AN XY: 134948
GnomAD4 exome AF: 0.000420 AC: 614AN: 1461172Hom.: 1 Cov.: 31 AF XY: 0.000411 AC XY: 299AN XY: 726896
GnomAD4 genome AF: 0.000361 AC: 55AN: 152274Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20AN XY: 74442
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 02, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | MYH14: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 22, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 02, 2013 | 1115-4C>T in intron 10 of MYH14: This variant is not expected to have clinical s ignificance because it is not located within the splice consensus sequence and i t has been identified in 0.01% (1/8468) of European American chromosomes and 0.0 2% (1/4214) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs142696359) . - |
Autosomal dominant nonsyndromic hearing loss 4A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at