Genetic Variant NM_014587.5:c.422+9C>G (chr16-982353-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 3033626.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 417 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX8	NM_014587.5 link	c.422+9C>G		intron_variant	Intron 1 of 2	ENST00000293894.4	NP_055402.2	P57073

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX8	ENST00000293894.4 link	c.422+9C>G		intron_variant	Intron 1 of 2	1	NM_014587.5	ENSP00000293894.3		P57073
SOX8	ENST00000566034.1 link	n.268C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

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

GnomAD3 exomes

AF:

0.000666

AC:

AN:

45042

Hom.:

AF XY:

0.000320

AC XY:

AN XY:

25022

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 SAS 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

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.000591

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000614

Gnomad4 OTH exome

AF:

0.000520

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152314

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

200

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00962

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Bravo

AF:

0.00335

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SOX8-related disorder

Benign:1

Jun 14, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.2

DANN

Benign

0.39

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