chr10-26174309-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017433.5(MYO3A):āc.4045G>Cā(p.Ala1349Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A1349A) has been classified as Likely benign.
Frequency
Consequence
NM_017433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.4045G>C | p.Ala1349Pro | missense_variant | 30/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.4045G>C | p.Ala1349Pro | missense_variant | 30/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1777-37534G>C | intron_variant | 1 | |||||
MYO3A | ENST00000647478.1 | c.*1393+3770G>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251352Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135842
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461826Hom.: 0 Cov.: 35 AF XY: 0.0000289 AC XY: 21AN XY: 727202
GnomAD4 genome AF: 0.000230 AC: 35AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 45812). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs149521185, gnomAD 0.08%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1349 of the MYO3A protein (p.Ala1349Pro). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | The c.4045G>C (p.A1349P) alteration is located in exon 30 (coding exon 28) of the MYO3A gene. This alteration results from a G to C substitution at nucleotide position 4045, causing the alanine (A) at amino acid position 1349 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 19, 2013 | Ala1349Pro in exon 30 of MYO3A: This variant is not expected to have clinical si gnificance because it is has been identified in 0.1% (5/4406) of African America n chromosomes from a broad population by the NHLBI Exome sequencing project (htt p://evs.gs.washington.edu/EVS/; dbSNP rs149521185). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at