Genetic Variant NM_005634.3:c.717_737delCGCTGCCGCGGCCGCAGCCGC (chrX-140504323-AGCGGCTGCGGCCGCGGCAGCG-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2

The NM_005634.3(SOX3):c.717_737delCGCTGCCGCGGCCGCAGCCGC(p.Ala240_Ala246del) variant causes a disruptive 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.32

Variant links:

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]

SOX3 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX3	NM_005634.3 link	c.717_737delCGCTGCCGCGGCCGCAGCCGC	p.Ala240_Ala246del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000370536.5	NP_005625.2	P41225

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX3	ENST00000370536.5 link	c.717_737delCGCTGCCGCGGCCGCAGCCGC	p.Ala240_Ala246del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005634.3	ENSP00000359567.2		P41225

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

100806

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

AN XY:

28608

show subpopulations

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:

AN:

35250

Hom.:

AF XY:

0.00103

AC XY:

AN XY:

8724

show subpopulations

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.:

AF XY:

0.000304

AC XY:

AN XY:

299587

show subpopulations

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:

AN:

100843

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

28649

show subpopulations

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.:

Bravo

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 07, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over