rs73637709

Positions:

• chrX-140504934-C-G
• chrX-140504934-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005634.3(SOX3):​c.127G>C​(p.Ala43Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,085,595 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: SOX3 NM_005634.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06827885).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX3	NM_005634.3	c.127G>C	p.Ala43Pro	missense_variant	1/1	ENST00000370536.5	NP_005625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX3	ENST00000370536.5	c.127G>C	p.Ala43Pro	missense_variant	1/1		NM_005634.3	ENSP00000359567	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000669 AC: 1 AN: 149416 Hom.: 0 AF XY: 0.0000211 AC XY: 1 AN XY: 47296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000879

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000368 AC: 4 AN: 1085595 Hom.: 0 Cov.: 33 AF XY: 0.00000563 AC XY: 2 AN XY: 355355

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000344

Gnomad4 SAS exome AF: 0.0000383

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.72
DANN	Benign	0.79
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.068	T
MetaSVM	Uncertain	0.0075	D
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.23
Sift	Benign	0.62	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.20		Gain of glycosylation at A43 (P = 0.0062);
MVP		0.30
ClinPred		0.014	T
GERP RS		0.84
Varity_R		0.078
gMVP		0.16

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: rs73637709; hg19: chrX-139587099;