NM_006941.4:c.*475G>A

Variant names:

• chr22-37973020-C-T
• rs139883
• NM_006941.4:c.*475G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006941.4(SOX10):​c.*475G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 156,852 control chromosomes in the GnomAD database, including 27,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26935 hom., cov: 32)
  • Exomes 𝑓: 0.62 (971 hom.)
• Consequence: SOX10 NM_006941.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.50
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-37973020-C-T is Benign according to our data. Variant chr22-37973020-C-T is described in ClinVar as Benign. ClinVar VariationId is 341614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 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.*475G>A		3_prime_UTR	Exon 4 of 4	NP_008872.1
	POLR2F	NM_001301130.2		c.293+5850C>T		intron	N/A	NP_001288059.1
	POLR2F	NM_001363825.1		c.*38+710C>T		intron	N/A	NP_001350754.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX10	ENST00000396884.8	TSL:1 MANE Select	c.*475G>A		3_prime_UTR	Exon 4 of 4	ENSP00000380093.2
	SOX10	ENST00000360880.6	TSL:1	c.*475G>A		3_prime_UTR	Exon 5 of 5	ENSP00000354130.2
	SOX10	ENST00000698177.1		c.*475G>A		3_prime_UTR	Exon 5 of 5	ENSP00000513596.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90021 AN: 151876 Hom.: 26935 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.624 AC: 3030 AN: 4858 Hom.: 971 Cov.: 0 AF XY: 0.626 AC XY: 1589 AN XY: 2538

African (AFR) AF: 0.481 AC: 50 AN: 104

American (AMR) AF: 0.614 AC: 405 AN: 660

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 54 AN: 96

East Asian (EAS) AF: 0.771 AC: 91 AN: 118

South Asian (SAS) AF: 0.645 AC: 142 AN: 220

European-Finnish (FIN) AF: 0.678 AC: 80 AN: 118

Middle Eastern (MID) AF: 0.500 AC: 5 AN: 10

European-Non Finnish (NFE) AF: 0.628 AC: 2062 AN: 3286

Other (OTH) AF: 0.573 AC: 141 AN: 246

GnomAD4 genome AF: 0.592 AC: 90055 AN: 151994 Hom.: 26935 Cov.: 32 AF XY: 0.592 AC XY: 43990 AN XY: 74302

African (AFR) AF: 0.506 AC: 20985 AN: 41450

American (AMR) AF: 0.603 AC: 9207 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2043 AN: 3466

East Asian (EAS) AF: 0.747 AC: 3856 AN: 5164

South Asian (SAS) AF: 0.623 AC: 3001 AN: 4820

European-Finnish (FIN) AF: 0.615 AC: 6504 AN: 10576

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42522 AN: 67942

Other (OTH) AF: 0.592 AC: 1244 AN: 2102

Alfa AF: 0.609 Hom.: 31570

Bravo AF: 0.588

Asia WGS AF: 0.654 AC: 2275 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.60
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs139883; hg19: chr22-38369027;