chr19-50244277-G-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP3BP4_StrongBP6BS1BS2
The NM_001145809.2(MYH14):c.1150G>T(p.Gly384Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,613,848 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001145809.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MYH14 | NM_001145809.2 | c.1150G>T | p.Gly384Cys | missense_variant | Exon 11 of 43 | ENST00000642316.2 | NP_001139281.1 | |
MYH14 | NM_001077186.2 | c.1150G>T | p.Gly384Cys | missense_variant | Exon 11 of 42 | NP_001070654.1 | ||
MYH14 | NM_024729.4 | c.1126G>T | p.Gly376Cys | missense_variant | Exon 10 of 41 | NP_079005.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00301 AC: 457AN: 152060Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00304 AC: 757AN: 248750Hom.: 5 AF XY: 0.00321 AC XY: 434AN XY: 135002
GnomAD4 exome AF: 0.00382 AC: 5578AN: 1461670Hom.: 22 Cov.: 32 AF XY: 0.00380 AC XY: 2761AN XY: 727118
GnomAD4 genome AF: 0.00300 AC: 457AN: 152178Hom.: 0 Cov.: 31 AF XY: 0.00277 AC XY: 206AN XY: 74386
ClinVar
Submissions by phenotype
not provided Benign:8
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This variant is associated with the following publications: (PMID: 27391121, 25262649, 30622556, 15015131, 27884173, 25098841, 30245029, 31898538) -
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MYH14: BS2 -
not specified Benign:3
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p.Gly384Cys in exon 11 of MYH14: This variant is not expected to have clinical s ignificance, because it has been identified in 1.3% (136/10142) of Ashkenazi Jew ish chromosomes including 1 homozygote by the Genome Aggregation Database (gnomA D, http://gnomad.broadinstitute.org/; dbSNP rs119103280). Although this variant has been reported as a de novo variant in one individual with moderate sensorine ural hearing loss (Donaudy 2004), the evidence is not sufficient to establish ca usality. -
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Autosomal dominant nonsyndromic hearing loss 4A Pathogenic:1Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome Benign:1
European Non-Finnish population allele frequency is 0.3994% (rs119103280, 511/127.956 alleles, 1 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as LIKELY BENIGN. Following criteria are met: BS1 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at