rs748467720

chrX-140504323-AGCGGCTGCGGCCGCGGCAGCG-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_005634.3(SOX3):c.717_737del(p.Ala242_Ala248del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,045,128 control chromosomes in the GnomAD database, including 5 homozygotes. There are 98 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., 7 hem., cov: 23)
  • Exomes 𝑓: 0.00029 (5 hom. 91 hem.)
• Consequence: SOX3 NM_005634.3 inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.32

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 -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005634.3
• BP6: Variant X-140504323-AGCGGCTGCGGCCGCGGCAGCG-A is Benign according to our data. Variant chrX-140504323-AGCGGCTGCGGCCGCGGCAGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 436840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-140504323-AGCGGCTGCGGCCGCGGCAGCG-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX3	NM_005634.3	c.717_737del	p.Ala242_Ala248del	inframe_deletion	1/1	ENST00000370536.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX3	ENST00000370536.5	c.717_737del	p.Ala242_Ala248del	inframe_deletion	1/1		NM_005634.3	P1

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 18 AN: 100806 Hom.: 0 Cov.: 23 AF XY: 0.000245 AC XY: 7 AN XY: 28608

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000205

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: 0.000244

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000652 AC: 23 AN: 35250 Hom.: 2 AF XY: 0.00103 AC XY: 9 AN XY: 8724

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000803

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00140

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.000290 AC: 274 AN: 944285 Hom.: 5 AF XY: 0.000304 AC XY: 91 AN XY: 299587

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000292

Gnomad4 ASJ exome AF: 0.0000737

Gnomad4 EAS exome AF: 0.000818

Gnomad4 SAS exome AF: 0.0000898

Gnomad4 FIN exome AF: 0.0000925

Gnomad4 NFE exome AF: 0.000311

Gnomad4 OTH exome AF: 0.000154

GnomAD4 genome AF: 0.000178 AC: 18 AN: 100843 Hom.: 0 Cov.: 23 AF XY: 0.000244 AC XY: 7 AN XY: 28649

Gnomad4 AFR AF: 0.000147

Gnomad4 AMR AF: 0.000204

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000244

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000427 Hom.: 2

Bravo AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 07, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs748467720; hg19: chrX-139586488;