16-981954-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014587.5(SOX8):c.32C>T(p.Pro11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,427,396 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 22 hom. )

Consequence

SOX8
NM_014587.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.77

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

SOX8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060388446).

BP6

Variant 16-981954-C-T is Benign according to our data. Variant chr16-981954-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645867.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 695 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014587.5. 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
	SOX8	NM_014587.5	MANE Select	c.32C>T	p.Pro11Leu	missense	Exon 1 of 3	NP_055402.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOX8	ENST00000293894.4	TSL:1 MANE Select	c.32C>T	p.Pro11Leu	missense	Exon 1 of 3	ENSP00000293894.3	P57073
SOX8	ENST00000711628.1		c.32C>T	p.Pro11Leu	missense	Exon 1 of 3	ENSP00000518816.1	A0AAA9YHU3
SOX8	ENST00000711625.1		c.32C>T	p.Pro11Leu	missense	Exon 1 of 3	ENSP00000518813.1	A0AAA9YHN4

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

698

AN:

150362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00899

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000503

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00745

Gnomad OTH

AF:

0.00388

GnomAD2 exomes

AF:

0.00400

AC:

482

AN:

120524

AF XY:

0.00423

show subpopulations

Gnomad AFR exome

AF:

0.000891

Gnomad AMR exome

AF:

0.00262

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000625

Gnomad NFE exome

AF:

0.00556

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00555

AC:

7091

AN:

1276926

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

3505

AN XY:

633362

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

25932

American (AMR)

AF:

0.00272

AC:

AN:

27586

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

244

AN:

20706

East Asian (EAS)

AF:

0.00

AC:

AN:

26884

South Asian (SAS)

AF:

0.00113

AC:

AN:

68782

European-Finnish (FIN)

AF:

0.000633

AC:

AN:

31594

Middle Eastern (MID)

AF:

0.00579

AC:

AN:

3454

European-Non Finnish (NFE)

AF:

0.00619

AC:

6322

AN:

1021494

Other (OTH)

AF:

0.00596

AC:

301

AN:

50494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

369

738

1106

1475

1844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.00462

AC:

695

AN:

150470

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

325

AN XY:

73506

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41350

American (AMR)

AF:

0.00634

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00899

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000503

AC:

AN:

9936

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00743

AC:

501

AN:

67392

Other (OTH)

AF:

0.00384

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00171

Hom.:

Bravo

AF:

0.00460

ESP6500AA

AF:

0.00119

AC:

ESP6500EA

AF:

0.00400

AC:

ExAC

AF:

0.00338

AC:

368

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

SOX8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

0.010

Eigen_PC

Benign

-0.0045

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.6

PhyloP100

1.8

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.0

REVEL

Benign

0.18

Sift

Uncertain

0.020

Sift4G

Uncertain

0.030

Polyphen

0.96

Vest4

0.14

MVP

0.57

MPC

2.4

ClinPred

0.011

GERP RS

3.4

PromoterAI

-0.038

Neutral

(source)

Varity_R

0.13

gMVP

0.36

Mutation Taster

=96/4

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