rs748467720

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

46,XX sex reversal 3
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
intellectual disability, X-linked, with panhypopituitarism
Inheritance: XL Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, G2P
panhypopituitarism, X-linked
Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder
Inheritance: XL Classification: MODERATE Submitted by: ClinGen
46,XX sex reversal 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
septooptic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
panhypopituitarism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
X-linked congenital generalized hypertrichosis
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability with isolated growth hormone deficiency
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
46,XX ovotesticular disorder of sex development
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

SOX3 links:

ENSG00000303910 (HGNC:):

ENSG00000303910 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 436840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 7 XL,AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005634.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX3	NM_005634.3	MANE Select	c.717_737delCGCTGCCGCGGCCGCAGCCGC	p.Ala240_Ala246del	disruptive_inframe_deletion	Exon 1 of 1	NP_005625.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SOX3	ENST00000370536.5	TSL:6 MANE Select	c.717_737delCGCTGCCGCGGCCGCAGCCGC	p.Ala240_Ala246del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000359567.2
ENSG00000303910	ENST00000797999.1		n.105+481_105+501delTGCGGCCGCGGCAGCGGCGGC		intron	N/A
ENSG00000303910	ENST00000798000.1		n.158+705_158+725delTGCGGCCGCGGCAGCGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

100806

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000652

AC:

AN:

35250

AF XY:

0.00103

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 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

African (AFR)

AF:

0.00

AC:

AN:

19336

American (AMR)

AF:

0.000292

AC:

AN:

10286

Ashkenazi Jewish (ASJ)

AF:

0.0000737

AC:

AN:

13571

East Asian (EAS)

AF:

0.000818

AC:

AN:

21992

South Asian (SAS)

AF:

0.0000898

AC:

AN:

33403

European-Finnish (FIN)

AF:

0.0000925

AC:

AN:

32435

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3242

European-Non Finnish (NFE)

AF:

0.000311

AC:

240

AN:

771055

Other (OTH)

AF:

0.000154

AC:

AN:

38965

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000178

AC:

AN:

100843

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

28649

show subpopulations

African (AFR)

AF:

0.000147

AC:

AN:

27123

American (AMR)

AF:

0.000204

AC:

AN:

9780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2446

East Asian (EAS)

AF:

0.00

AC:

AN:

3051

South Asian (SAS)

AF:

0.00

AC:

AN:

2236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.000244

AC:

AN:

49248

Other (OTH)

AF:

0.00

AC:

AN:

1335

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=193/7

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over