X-140504074-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005634.3(SOX3):c.987C>T(p.Ala329Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000202 in 991,301 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000011 ( 0 hom. 0 hem. )

Consequence

SOX3
NM_005634.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.479

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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-140504074-G-A is Benign according to our data. Variant chrX-140504074-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 755811.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.479 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX3	NM_005634.3	MANE Select	c.987C>T	p.Ala329Ala	synonymous	Exon 1 of 1	NP_005625.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOX3	ENST00000370536.5	TSL:6 MANE Select	c.987C>T	p.Ala329Ala	synonymous	Exon 1 of 1	ENSP00000359567.2	P41225
ENSG00000303910	ENST00000797999.1		n.105+226G>A		intron	N/A
ENSG00000303910	ENST00000798000.1		n.158+450G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000914

AC:

AN:

109386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000113

AC:

AN:

881915

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

273587

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19114

American (AMR)

AF:

0.00

AC:

AN:

11778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12451

East Asian (EAS)

AF:

0.00

AC:

AN:

20141

South Asian (SAS)

AF:

0.00

AC:

AN:

24295

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3100

European-Non Finnish (NFE)

AF:

0.00000136

AC:

AN:

735371

Other (OTH)

AF:

0.00

AC:

AN:

36075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000914

AC:

AN:

109386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32602

show subpopulations

African (AFR)

AF:

0.0000330

AC:

AN:

30288

American (AMR)

AF:

0.00

AC:

AN:

10524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2616

East Asian (EAS)

AF:

0.00

AC:

AN:

3403

South Asian (SAS)

AF:

0.00

AC:

AN:

2657

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52140

Other (OTH)

AF:

0.00

AC:

AN:

1472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.5

(source)

DANN

Benign

0.83

PhyloP100

0.48

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

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

Computational scores

Splicing

Publications

Other links and lift over