NM_005634.3:c.1056C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_005634.3(SOX3):c.1056C>A(p.Pro352Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 988,065 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000014 ( 0 hom. 5 hem. )

Consequence

SOX3
NM_005634.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.00

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant X-140504005-G-T is Benign according to our data. Variant chrX-140504005-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3041100.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 4 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.1056C>A	p.Pro352Pro	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.1056C>A	p.Pro352Pro	synonymous	Exon 1 of 1	ENSP00000359567.2	P41225
ENSG00000303910	ENST00000797999.1		n.105+157G>T		intron	N/A
ENSG00000303910	ENST00000798000.1		n.158+381G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000128

AC:

AN:

109647

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00104

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:

0.0000192

Gnomad OTH

AF:

0.00135

GnomAD2 exomes

AF:

0.00

AC:

AN:

13336

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:

0.0000137

AC:

AN:

878389

Hom.:

Cov.:

AF XY:

0.0000187

AC XY:

AN XY:

266903

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18414

American (AMR)

AF:

0.000888

AC:

AN:

7884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12330

East Asian (EAS)

AF:

0.00

AC:

AN:

20667

South Asian (SAS)

AF:

0.00

AC:

AN:

25184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20669

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2335

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

734697

Other (OTH)

AF:

0.0000829

AC:

AN:

36209

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.000128

AC:

AN:

109676

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

32630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30467

American (AMR)

AF:

0.00104

AC:

AN:

10572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2621

East Asian (EAS)

AF:

0.00

AC:

AN:

3403

South Asian (SAS)

AF:

0.00

AC:

AN:

2625

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

52173

Other (OTH)

AF:

0.00134

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.00

Hom.:

Bravo

AF:

0.000234

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SOX3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.3

(source)

DANN

Benign

0.80

PhyloP100

1.0

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