Genetic Variant SOX21:p.Leu86Leu (chr13-94711792-C-G) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_007084.4(SOX21):c.258G>C(p.Leu86Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,613,222 control chromosomes in the GnomAD database, including 145,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12666 hom., cov: 32)

Exomes 𝑓: 0.42 ( 132791 hom. )

Consequence

SOX21
NM_007084.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.81

Publications

16 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 13-94711792-C-G is Benign according to our data. Variant chr13-94711792-C-G is described in ClinVar as Benign. ClinVar VariationId is 1268771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

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.258G>C	p.Leu86Leu	synonymous	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.258G>C	p.Leu86Leu	synonymous	Exon 1 of 1	ENSP00000366144.2	Q9Y651
	SOX21-AS1	ENST00000665450.1		n.132+8207C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60690

AN:

151568

Hom.:

12658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.356

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.402

GnomAD2 exomes

AF:

0.424

AC:

106373

AN:

250968

AF XY:

0.423

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.446

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.488

Gnomad FIN exome

AF:

0.557

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.424

AC:

620211

AN:

1461538

Hom.:

132791

Cov.:

AF XY:

0.422

AC XY:

307116

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.298

AC:

9986

AN:

33462

American (AMR)

AF:

0.444

AC:

19860

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

11261

AN:

26126

East Asian (EAS)

AF:

0.510

AC:

20243

AN:

39662

South Asian (SAS)

AF:

0.342

AC:

29494

AN:

86250

European-Finnish (FIN)

AF:

0.551

AC:

29407

AN:

53340

Middle Eastern (MID)

AF:

0.377

AC:

2171

AN:

5766

European-Non Finnish (NFE)

AF:

0.425

AC:

472573

AN:

1111860

Other (OTH)

AF:

0.418

AC:

25216

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

23489

46978

70466

93955

117444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14410

28820

43230

57640

72050

<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:

0.400

AC:

60715

AN:

151684

Hom.:

12666

Cov.:

AF XY:

0.405

AC XY:

30025

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.298

AC:

12345

AN:

41434

American (AMR)

AF:

0.415

AC:

6344

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1515

AN:

3468

East Asian (EAS)

AF:

0.475

AC:

2398

AN:

5046

South Asian (SAS)

AF:

0.335

AC:

1617

AN:

4824

European-Finnish (FIN)

AF:

0.570

AC:

5993

AN:

10510

Middle Eastern (MID)

AF:

0.359

AC:

104

AN:

290

European-Non Finnish (NFE)

AF:

0.429

AC:

29118

AN:

67828

Other (OTH)

AF:

0.400

AC:

843

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1861

3722

5583

7444

9305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.420

Hom.:

4445

Bravo

AF:

0.392

Asia WGS

AF:

0.393

AC:

1367

AN:

3478

EpiCase

AF:

0.428

EpiControl

AF:

0.427

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

1.8

Mutation Taster

=97/3

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over