22-37983594-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_006941.4(SOX10):​c.191A>G​(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

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.05
Variant links:
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]

Genome browser will be placed here

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
SOX10NM_006941.4 linkc.191A>G p.Asp64Gly missense_variant Exon 2 of 4 ENST00000396884.8 NP_008872.1 P56693-1A0A024R1N6
POLR2FNM_001301130.2 linkc.294-2560T>C intron_variant Intron 4 of 5 NP_001288059.1 B0QYL9
POLR2FNM_001363825.1 linkc.*38+11284T>C intron_variant Intron 5 of 5 NP_001350754.1
POLR2FNM_001301131.2 linkc.293+16424T>C intron_variant Intron 4 of 4 NP_001288060.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOX10ENST00000396884.8 linkc.191A>G p.Asp64Gly missense_variant Exon 2 of 4 1 NM_006941.4 ENSP00000380093.2 P56693-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000830
AC:
2
AN:
240888
Hom.:
0
AF XY:
0.00000763
AC XY:
1
AN XY:
131108
show subpopulations
Gnomad AFR exome
AF:
0.0000649
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000333
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456802
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
724802
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.82
D;D;D
Eigen
Benign
-0.085
Eigen_PC
Benign
0.071
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.78
.;T;T
M_CAP
Pathogenic
0.95
D
MetaRNN
Uncertain
0.68
D;D;D
MetaSVM
Pathogenic
0.81
D
MutationAssessor
Benign
1.9
L;L;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-2.7
D;D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0080
D;D;D
Sift4G
Uncertain
0.040
D;D;.
Polyphen
0.0040
B;B;.
Vest4
0.38
MVP
0.86
MPC
1.3
ClinPred
0.65
D
GERP RS
4.4
Varity_R
0.50
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372400283; hg19: chr22-38379601; API