X-140504005-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_005634.3(SOX3):​c.1056C>A​(p.Pro352=) 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

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.00
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOX3NM_005634.3 linkuse as main transcriptc.1056C>A p.Pro352= synonymous_variant 1/1 ENST00000370536.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOX3ENST00000370536.5 linkuse as main transcriptc.1056C>A p.Pro352= synonymous_variant 1/1 NM_005634.3 P1

Frequencies

GnomAD3 genomes
AF:
0.000128
AC:
14
AN:
109647
Hom.:
0
Cov.:
23
AF XY:
0.000123
AC XY:
4
AN XY:
32587
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
GnomAD4 exome
AF:
0.0000137
AC:
12
AN:
878389
Hom.:
0
Cov.:
22
AF XY:
0.0000187
AC XY:
5
AN XY:
266903
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000888
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000272
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.000128
AC:
14
AN:
109676
Hom.:
0
Cov.:
23
AF XY:
0.000123
AC XY:
4
AN XY:
32630
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00104
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000192
Gnomad4 OTH
AF:
0.00134
Bravo
AF:
0.000234

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SOX3-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 28, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
9.3
DANN
Benign
0.80

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

LitVar

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

Other links and lift over

dbSNP: rs768259292; hg19: chrX-139586170; API