chr2-5692816-T-G

Position:

• chr2-5692816-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003108.4(SOX11):​c.95T>G​(p.Val32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOX11 NM_003108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22

Genes affected

SOX11 (HGNC:11191): (SRY-box transcription factor 11) This intronless 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 regulator after forming a protein complex with other proteins. The protein may function in the developing nervous system and play a role in tumorigenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26581237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX11	NM_003108.4	c.95T>G	p.Val32Gly	missense_variant	1/1	ENST00000322002.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX11	ENST00000322002.5	c.95T>G	p.Val32Gly	missense_variant	1/1		NM_003108.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.95T>G (p.V32G) alteration is located in exon 1 (coding exon 1) of the SOX11 gene. This alteration results from a T to G substitution at nucleotide position 95, causing the valine (V) at amino acid position 32 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	0.87	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.11	B
Vest4		0.18
MutPred		0.35		Gain of disorder (P = 0.0122);
MVP		0.94
MPC		2.0
ClinPred		0.79	D
GERP RS		1.9
Varity_R		0.19
gMVP		0.94

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

Other links and lift over

dbSNP: rs1572216212; hg19: chr2-5832948; COSMIC: COSV58987598; COSMIC: COSV58987598;