22-37983594-T-C
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_006941.4(SOX10):āc.191A>Gā(p.Asp64Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,608,940 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
SOX10
NM_006941.4 missense
NM_006941.4 missense
Scores
5
8
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.05
Genes affected
SOX10 (HGNC:11190): (SRY-box transcription factor 10) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development. Mutations in this gene are associated with Waardenburg-Shah and Waardenburg-Hirschsprung disease. [provided by RefSeq, Jul 2008]
POLR2F (HGNC:9193): (RNA polymerase II, I and III subunit F) This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BS2
High AC in GnomAd4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SOX10 | NM_006941.4 | c.191A>G | p.Asp64Gly | missense_variant | Exon 2 of 4 | ENST00000396884.8 | NP_008872.1 | |
POLR2F | NM_001301130.2 | c.294-2560T>C | intron_variant | Intron 4 of 5 | NP_001288059.1 | |||
POLR2F | NM_001363825.1 | c.*38+11284T>C | intron_variant | Intron 5 of 5 | NP_001350754.1 | |||
POLR2F | NM_001301131.2 | c.293+16424T>C | intron_variant | Intron 4 of 4 | NP_001288060.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152138Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000830 AC: 2AN: 240888Hom.: 0 AF XY: 0.00000763 AC XY: 1AN XY: 131108
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1456802Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 724802
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74316
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;.
Polyphen
B;B;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at