Genetic Variant SOX8:p.Ser14Ser (chr16-981964-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_014587.5(SOX8):c.42C>T(p.Ser14Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,439,036 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

SOX8
NM_014587.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.860

Variant links:

Genes affected

SOX8 (HGNC:11203): (SRY-box transcription factor 8) This 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 activator after forming a protein complex with other proteins. This protein may be involved in brain development and function. Haploinsufficiency for this protein may contribute to the cognitive disability found in an alpha-thalassemia-related syndrome (ART-16). This protein is also highly expressed in the majority of human hepatocellular carcinomas and promotes cellular proliferation and enhanced tumor growth. [provided by RefSeq, Jul 2017]

SOX8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 16-981964-C-T is Benign according to our data. Variant chr16-981964-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.86 with no splicing effect.

BS2

High AC in GnomAd4 at 379 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX8	NM_014587.5 link	c.42C>T	p.Ser14Ser	synonymous_variant	Exon 1 of 3	ENST00000293894.4	NP_055402.2	P57073

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX8	ENST00000293894.4 link	c.42C>T	p.Ser14Ser	synonymous_variant	Exon 1 of 3	1	NM_014587.5	ENSP00000293894.3		P57073
SOX8	ENST00000566034.1 link	n.-122C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

379

AN:

150546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00238

Gnomad ASJ

AF:

0.00203

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00451

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00368

Gnomad OTH

AF:

0.00243

GnomAD3 exomes

AF:

0.00293

AC:

368

AN:

125426

Hom.:

AF XY:

0.00297

AC XY:

216

AN XY:

72832

show subpopulations

Gnomad AFR exome

AF:

0.000424

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00197

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000509

Gnomad FIN exome

AF:

0.00436

Gnomad NFE exome

AF:

0.00484

Gnomad OTH exome

AF:

0.00206

GnomAD4 exome

AF:

0.00283

AC:

3651

AN:

1288382

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

1843

AN XY:

639390

show subpopulations

Gnomad4 AFR exome

AF:

0.000914

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000426

Gnomad4 FIN exome

AF:

0.00455

Gnomad4 NFE exome

AF:

0.00320

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00252

AC:

379

AN:

150654

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

185

AN XY:

73598

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00238

Gnomad4 ASJ

AF:

0.00203

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00451

Gnomad4 NFE

AF:

0.00368

Gnomad4 OTH

AF:

0.00240

Alfa

AF:

0.00381

Hom.:

Bravo

AF:

0.00212

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SOX8: BP4, BP7 -

Apr 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.84

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