Genetic Variant SOX21:p.Ala273Ser (chr13-94711233-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_007084.4(SOX21):c.817G>T(p.Ala273Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A273T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOX21
NM_007084.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.91

Publications

0 publications found

Variant links:

Genes affected

SOX21 (HGNC:11197): (SRY-box transcription factor 21) SRY-related HMG-box (SOX) genes encode a family of DNA-binding proteins containing a 79-amino acid HMG (high mobility group) domain that shares at least 50% sequence identity with the DNA-binding HMG box of the SRY protein (MIM 480000). SOX proteins are divided into 6 subgroups based on sequence similarity within and outside of the HMG domain. For additional background information on SOX genes, see SOX1 (MIM 602148).[supplied by OMIM, Apr 2004]

SOX21 links:

SOX21-AS1 (HGNC:39807): (SOX21 antisense divergent transcript 1)

SOX21-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32383046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007084.4. 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
	SOX21	NM_007084.4	MANE Select	c.817G>T	p.Ala273Ser	missense	Exon 1 of 1	NP_009015.1	Q9Y651

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX21	ENST00000376945.4	TSL:6 MANE Select	c.817G>T	p.Ala273Ser	missense	Exon 1 of 1	ENSP00000366144.2	Q9Y651
	SOX21-AS1	ENST00000665450.1		n.132+7648C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1203752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

587394

African (AFR)

AF:

0.00

AC:

AN:

24332

American (AMR)

AF:

0.00

AC:

AN:

12186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17486

East Asian (EAS)

AF:

0.00

AC:

AN:

27982

South Asian (SAS)

AF:

0.00

AC:

AN:

48454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3482

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

992036

Other (OTH)

AF:

0.00

AC:

AN:

48880

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.096

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.32

MetaSVM

Pathogenic

0.80

MutationAssessor

Benign

1.1

PhyloP100

4.9

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.55

REVEL

Uncertain

0.48

Sift

Benign

0.093

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.21

MutPred

0.31

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.87

ClinPred

0.75

GERP RS

3.9

Varity_R

0.15

gMVP

0.52

Mutation Taster

=74/26

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over