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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX21	NM_007084.4 link	c.258G>C	p.Leu86Leu	synonymous_variant	Exon 1 of 1	ENST00000376945.4	NP_009015.1	Q9Y651

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX21	ENST00000376945.4 link	c.258G>C	p.Leu86Leu	synonymous_variant	Exon 1 of 1	6	NM_007084.4	ENSP00000366144.2		Q9Y651
SOX21-AS1	ENST00000665450.1 link	n.132+8207C>G		intron_variant	Intron 1 of 3

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

GnomAD3 exomes

AF:

0.424

AC:

106373

AN:

250968

Hom.:

23120

AF XY:

0.423

AC XY:

57438

AN XY:

135686

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 SAS exome

AF:

0.333

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

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.444

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.510

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.551

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.400

AC:

60715

AN:

151684

Hom.:

12666

Cov.:

AF XY:

0.405

AC XY:

30025

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.415

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.335

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.400

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 13, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.92

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