rs34393601
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_002470.4(MYH3):c.5254G>T(p.Ala1752Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000366 in 1,614,122 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1752T) has been classified as Benign.
Frequency
Consequence
NM_002470.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.5254G>T | p.Ala1752Ser | missense_variant | 36/41 | ENST00000583535.6 | |
LOC124903927 | XR_007065620.1 | n.100C>A | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH3 | ENST00000583535.6 | c.5254G>T | p.Ala1752Ser | missense_variant | 36/41 | 5 | NM_002470.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00199 AC: 303AN: 152144Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000458 AC: 115AN: 251184Hom.: 0 AF XY: 0.000331 AC XY: 45AN XY: 135772
GnomAD4 exome AF: 0.000198 AC: 289AN: 1461860Hom.: 1 Cov.: 32 AF XY: 0.000165 AC XY: 120AN XY: 727226
GnomAD4 genome ? AF: 0.00198 AC: 302AN: 152262Hom.: 2 Cov.: 32 AF XY: 0.00184 AC XY: 137AN XY: 74450
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The MYH3 p.Ala1752Ser variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs34393601) and in control databases in 186 of 282568 chromosomes (1 homozygous) at a frequency of 0.000658 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 175 of 24958 chromosomes (freq: 0.007012), Other in 3 of 7220 chromosomes (freq: 0.000416), Latino in 4 of 35406 chromosomes (freq: 0.000113) and European (non-Finnish) in 4 of 129022 chromosomes (freq: 0.000031), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The p.Ala1752 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2020 | This variant is associated with the following publications: (PMID: 22519952) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at