rs149435516

Variant names:

• chr22-37983767-G-A
• rs149435516
• NM_006941.4:c.18C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37983767-G-A
• chr22-37983767-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006941.4(SOX10):​c.18C>T​(p.Asp6Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,474,910 control chromosomes in the GnomAD database, including 2,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (459 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2371 hom.)
• Consequence: SOX10 NM_006941.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 3.02
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 22-37983767-G-A is Benign according to our data. Variant chr22-37983767-G-A is described in ClinVar as Benign. ClinVar VariationId is 227078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX10	NM_006941.4	MANE Select	c.18C>T	p.Asp6Asp	synonymous	Exon 2 of 4	NP_008872.1	P56693-1
	POLR2F	NM_001301130.2		c.294-2387G>A		intron	N/A	NP_001288059.1	B0QYL9
	POLR2F	NM_001363825.1		c.*38+11457G>A		intron	N/A	NP_001350754.1	F8WC47

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX10	ENST00000396884.8	TSL:1 MANE Select	c.18C>T	p.Asp6Asp	synonymous	Exon 2 of 4	ENSP00000380093.2	P56693-1
	SOX10	ENST00000360880.6	TSL:1	c.18C>T	p.Asp6Asp	synonymous	Exon 3 of 5	ENSP00000354130.2	P56693-1
	SOX10	ENST00000698177.1		c.234C>T	p.Asp78Asp	synonymous	Exon 3 of 5	ENSP00000513596.1	A0A8V8TM01

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10602 AN: 151258 Hom.: 460 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0791

GnomAD2 exomes AF: 0.0554 AC: 5529 AN: 99714 AF XY: 0.0561

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0305

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.0498

Gnomad NFE exome AF: 0.0557

Gnomad OTH exome AF: 0.0574

GnomAD4 exome AF: 0.0581 AC: 76853 AN: 1323542 Hom.: 2371 Cov.: 32 AF XY: 0.0579 AC XY: 37801 AN XY: 653280

African (AFR) AF: 0.112 AC: 2974 AN: 26646

American (AMR) AF: 0.0343 AC: 986 AN: 28714

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 662 AN: 22772

East Asian (EAS) AF: 0.0890 AC: 2660 AN: 29900

South Asian (SAS) AF: 0.0662 AC: 4924 AN: 74378

European-Finnish (FIN) AF: 0.0517 AC: 1691 AN: 32738

Middle Eastern (MID) AF: 0.0492 AC: 208 AN: 4230

European-Non Finnish (NFE) AF: 0.0567 AC: 59570 AN: 1049948

Other (OTH) AF: 0.0586 AC: 3178 AN: 54216

GnomAD4 genome AF: 0.0701 AC: 10604 AN: 151368 Hom.: 459 Cov.: 32 AF XY: 0.0699 AC XY: 5171 AN XY: 73990

African (AFR) AF: 0.107 AC: 4436 AN: 41338

American (AMR) AF: 0.0464 AC: 706 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 100 AN: 3462

East Asian (EAS) AF: 0.0947 AC: 485 AN: 5122

South Asian (SAS) AF: 0.0632 AC: 304 AN: 4810

European-Finnish (FIN) AF: 0.0541 AC: 561 AN: 10370

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0552 AC: 3740 AN: 67744

Other (OTH) AF: 0.0811 AC: 170 AN: 2096

Alfa AF: 0.0357 Hom.: 43

Asia WGS AF: 0.0650 AC: 219 AN: 3366

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	not provided (3)
-	-	1	PCWH syndrome (1)
-	-	1	Waardenburg syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Uncertain	0.98
PhyloP100		3.0
PromoterAI		0.046	Neutral
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs149435516; hg19: chr22-38379774; COSMIC: COSV61004948; COSMIC: COSV61004948;