rs1178579710

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_005634.3(SOX3):c.1297G>T(p.Ala433Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,170,049 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000032 ( 0 hom. 10 hem. )

Consequence

SOX3
NM_005634.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.02

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.33886844).

BS2

High Hemizygotes in GnomAd4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX3	NM_005634.3	MANE Select	c.1297G>T	p.Ala433Ser	missense	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.1297G>T	p.Ala433Ser	missense	Exon 1 of 1	ENSP00000359567.2	P41225
ENSG00000303910	ENST00000797999.1		n.21C>A		non_coding_transcript_exon	Exon 1 of 5
ENSG00000303910	ENST00000798002.1		n.15C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112355

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

119587

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000321

AC:

AN:

1057694

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

339522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25914

American (AMR)

AF:

0.00

AC:

AN:

31264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18501

East Asian (EAS)

AF:

0.00

AC:

AN:

29131

South Asian (SAS)

AF:

0.0000201

AC:

AN:

49700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29023

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2923

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

826560

Other (OTH)

AF:

0.0000224

AC:

AN:

44678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000267

AC:

AN:

112355

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

34531

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31044

American (AMR)

AF:

0.00

AC:

AN:

10771

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3514

South Asian (SAS)

AF:

0.00

AC:

AN:

2701

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53123

Other (OTH)

AF:

0.00

AC:

AN:

1497

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.0000340

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Premature ovarian insufficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.3

PhyloP100

3.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.57

REVEL

Uncertain

0.37

Sift

Benign

0.26

Sift4G

Benign

0.39

Polyphen

1.0

Vest4

0.15

MVP

0.53

ClinPred

0.87

GERP RS

2.7

Varity_R

0.24

gMVP

0.65

Mutation Taster

=66/34

polymorphism

(source)

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