X-140504120-G-C

Position:

• chrX-140504120-G-C

Variant summary

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

The NM_005634.3(SOX3):​c.941C>G​(p.Pro314Arg) variant causes a missense change. 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: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SOX3 NM_005634.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

Genes affected

SOX3 (HGNC:11199): (SRY-box transcription factor 3) 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 regulator after forming a protein complex with other proteins. Mutations in this gene have been associated with X-linked cognitive disability with growth hormone deficiency. [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=0.35445714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX3	NM_005634.3	c.941C>G	p.Pro314Arg	missense_variant	1/1	ENST00000370536.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX3	ENST00000370536.5	c.941C>G	p.Pro314Arg	missense_variant	1/1		NM_005634.3	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 915436 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 284744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SOX3: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	0.0019	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.97	N
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.40	T
Polyphen		0.98	D
Vest4		0.30
MutPred		0.29		Gain of MoRF binding (P = 0.0027);
MVP		0.38
ClinPred		0.70	D
GERP RS		3.6
Varity_R		0.35
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-139586285;