X-140503972-GGCTGCGGCCGCA-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_005634.3(SOX3):c.1077_1088del(p.Ala361_Ala364del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,048,582 control chromosomes in the GnomAD database, including 1 homozygotes. There are 30 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000064 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00013 (1 hom. 28 hem.)
• Consequence: SOX3 NM_005634.3 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.44

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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005634.3
• BP6: Variant X-140503972-GGCTGCGGCCGCA-G is Benign according to our data. Variant chrX-140503972-GGCTGCGGCCGCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX3	NM_005634.3	c.1077_1088del	p.Ala361_Ala364del	inframe_deletion	1/1	ENST00000370536.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX3	ENST00000370536.5	c.1077_1088del	p.Ala361_Ala364del	inframe_deletion	1/1		NM_005634.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000640 AC: 7 AN: 109296 Hom.: 0 Cov.: 23 AF XY: 0.0000618 AC XY: 2 AN XY: 32374

Gnomad AFR AF: 0.0000331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000948

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: 0.0000961

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000803 AC: 4 AN: 49817 Hom.: 0 AF XY: 0.0000821 AC XY: 1 AN XY: 12185

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000154

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000128 AC: 120 AN: 939286 Hom.: 1 AF XY: 0.0000972 AC XY: 28 AN XY: 288012

Gnomad4 AFR exome AF: 0.0000487

Gnomad4 AMR exome AF: 0.0000687

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000435

Gnomad4 SAS exome AF: 0.000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.000231

GnomAD4 genome AF: 0.0000640 AC: 7 AN: 109296 Hom.: 0 Cov.: 23 AF XY: 0.0000618 AC XY: 2 AN XY: 32374

Gnomad4 AFR AF: 0.0000331

Gnomad4 AMR AF: 0.0000948

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000961

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000604

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

SOX3: BS2 -

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: rs756883263; hg19: chrX-139586137;