Genetic Variant NM_003107.3:c.63C>A (chr6-21594597-C-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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:

LINC00581 (HGNC:43840): (long intergenic non-protein coding RNA 581)

LINC00581 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3053451.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 92 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003107.3. 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
	SOX4	NM_003107.3	MANE Select	c.63C>A	p.Asp21Glu	missense	Exon 1 of 1	NP_003098.1	Q06945

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX4	ENST00000244745.4	TSL:6 MANE Select	c.63C>A	p.Asp21Glu	missense	Exon 1 of 1	ENSP00000244745.1	Q06945
	LINC00581	ENST00000637901.1	TSL:5	n.168+829G>T		intron	N/A

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

GnomAD2 exomes

AF:

0.000150

AC:

AN:

234024

AF XY:

0.000116

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 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

African (AFR)

AF:

0.00213

AC:

AN:

33396

American (AMR)

AF:

0.000202

AC:

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39538

South Asian (SAS)

AF:

0.00

AC:

AN:

85916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5174

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1110718

Other (OTH)

AF:

0.000117

AC:

AN:

60056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.000604

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41588

American (AMR)

AF:

0.000196

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

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:

0.0000957

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SOX4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

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

PhyloP100

1.5

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

Mutation Taster

=95/5

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