dbSNP rs201672745: SOX8:c.422+9C>G (chr16-982353-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_014587.5(SOX8):c.422+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000531 in 1,347,834 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

SOX8
NM_014587.5 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.42

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-982353-C-G is Benign according to our data. Variant chr16-982353-C-G is described in ClinVar as Benign. ClinVar VariationId is 3033626.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 417 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.422+9C>G		intron	N/A	NP_055402.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOX8	ENST00000293894.4	TSL:1 MANE Select	c.422+9C>G	intron	N/A	ENSP00000293894.3	P57073
SOX8	ENST00000711628.1		c.422+9C>G	intron	N/A	ENSP00000518816.1	A0AAA9YHU3
SOX8	ENST00000711625.1		c.422+9C>G	intron	N/A	ENSP00000518813.1	A0AAA9YHN4

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000666

AC:

AN:

45042

AF XY:

0.000320

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000434

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000250

AC:

299

AN:

1195520

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

126

AN XY:

578046

show subpopulations

African (AFR)

AF:

0.0106

AC:

260

AN:

24632

American (AMR)

AF:

0.000591

AC:

AN:

13528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16198

East Asian (EAS)

AF:

0.00

AC:

AN:

28822

South Asian (SAS)

AF:

0.00

AC:

AN:

44724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3328

European-Non Finnish (NFE)

AF:

0.00000614

AC:

AN:

977324

Other (OTH)

AF:

0.000520

AC:

AN:

48102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152314

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

200

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00962

AC:

400

AN:

41586

American (AMR)

AF:

0.000784

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

119

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:

0.00

Hom.:

Bravo

AF:

0.00335

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SOX8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.2

(source)

DANN

Benign

0.39

PhyloP100

1.4

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over