X-140504005-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005634.3(SOX3):c.1056C>A(p.Pro352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 988,065 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.000014 (0 hom. 5 hem.)
• Consequence: SOX3 NM_005634.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant X-140504005-G-T is Benign according to our data. Variant chrX-140504005-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041100.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX3	NM_005634.3	c.1056C>A	p.Pro352=	synonymous_variant	1/1	ENST00000370536.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX3	ENST00000370536.5	c.1056C>A	p.Pro352=	synonymous_variant	1/1		NM_005634.3	P1

Frequencies

GnomAD3 genomes AF: 0.000128 AC: 14 AN: 109647 Hom.: 0 Cov.: 23 AF XY: 0.000123 AC XY: 4 AN XY: 32587

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000192

Gnomad OTH AF: 0.00135

GnomAD4 exome AF: 0.0000137 AC: 12 AN: 878389 Hom.: 0 Cov.: 22 AF XY: 0.0000187 AC XY: 5 AN XY: 266903

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000888

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: 0.00000272

Gnomad4 OTH exome AF: 0.0000829

GnomAD4 genome AF: 0.000128 AC: 14 AN: 109676 Hom.: 0 Cov.: 23 AF XY: 0.000123 AC XY: 4 AN XY: 32630

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00104

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000192

Gnomad4 OTH AF: 0.00134

Bravo AF: 0.000234

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SOX3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	9.3
Dann	Benign	0.80

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: rs768259292; hg19: chrX-139586170;