Variant 6-21594597-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003107.3(SOX4):c.63C>A(p.Asp21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,609,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00060 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SOX4
NM_003107.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

SOX4 (HGNC:11200): (SRY-box transcription factor 4) This intronless 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, such as syndecan binding protein (syntenin). The protein may function in the apoptosis pathway leading to cell death as well as to tumorigenesis and may mediate downstream effects of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in bone development. The solution structure has been resolved for the HMG-box of a similar mouse protein. [provided by RefSeq, Jul 2008]

SOX4 links:

ENSG00000283480 (HGNC:):

ENSG00000283480 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018759847).

BP6

Variant 6-21594597-C-A is Benign according to our data. Variant chr6-21594597-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3053451.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX4	NM_003107.3 link	c.63C>A	p.Asp21Glu	missense_variant	Exon 1 of 1	ENST00000244745.4	NP_003098.1	Q06945

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX4	ENST00000244745.4 link	c.63C>A	p.Asp21Glu	missense_variant	Exon 1 of 1	6	NM_003107.3	ENSP00000244745.1		Q06945
ENSG00000283480	ENST00000637901.1 link	n.168+829G>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000478

GnomAD3 exomes

AF:

0.000150

AC:

AN:

234024

Hom.:

AF XY:

0.000116

AC XY:

AN XY:

129058

show subpopulations

Gnomad AFR exome

AF:

0.00236

Gnomad AMR exome

AF:

0.0000590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000632

AC:

AN:

1456732

Hom.:

Cov.:

AF XY:

0.0000497

AC XY:

AN XY:

724410

show subpopulations

Gnomad4 AFR exome

AF:

0.00213

Gnomad4 AMR exome

AF:

0.000202

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:

0.00000450

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000604

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000203

Hom.:

Bravo

AF:

0.000688

ESP6500AA

AF:

0.00164

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000117

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SOX4-related disorder

Benign:1

Apr 24, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.65

Eigen

Benign

-0.057

Eigen_PC

Benign

0.047

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.019

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

0.30

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.40

Sift

Benign

0.17

Sift4G

Benign

0.16

Polyphen

0.33

Vest4

0.15

MutPred

0.20

Loss of helix (P = 0.079);

MVP

0.90

MPC

1.1

ClinPred

0.11

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.27

gMVP

0.89

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over