Variant 8-54458236-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022454.4(SOX17):c.98C>A(p.Ala33Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,598,738 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0046 ( 20 hom. )

Consequence

SOX17
NM_022454.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.91

Variant links:

Genes affected

SOX17 (HGNC:18122): (SRY-box transcription factor 17) 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 regulator after forming a protein complex with other proteins. [provided by RefSeq, Jul 2008]

SOX17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009690851).

BP6

Variant 8-54458236-C-A is Benign according to our data. Variant chr8-54458236-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1601523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 496 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX17	NM_022454.4 linkuse as main transcript	c.98C>A	p.Ala33Asp	missense_variant	1/2	ENST00000297316.5	NP_071899.1	Q9H6I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX17	ENST00000297316.5 linkuse as main transcript	c.98C>A	p.Ala33Asp	missense_variant	1/2	1	NM_022454.4	ENSP00000297316.4		Q9H6I2

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

496

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00467

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00356

AC:

738

AN:

207176

Hom.:

AF XY:

0.00374

AC XY:

428

AN XY:

114468

show subpopulations

Gnomad AFR exome

AF:

0.000875

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.00446

Gnomad NFE exome

AF:

0.00477

Gnomad OTH exome

AF:

0.00383

GnomAD4 exome

AF:

0.00459

AC:

6645

AN:

1446410

Hom.:

Cov.:

AF XY:

0.00469

AC XY:

3366

AN XY:

718330

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.000194

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00545

Gnomad4 FIN exome

AF:

0.00528

Gnomad4 NFE exome

AF:

0.00502

Gnomad4 OTH exome

AF:

0.00453

GnomAD4 genome

AF:

0.00326

AC:

496

AN:

152328

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

229

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00385

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00467

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00373

Hom.:

Bravo

AF:

0.00307

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00192

AC:

ESP6500EA

AF:

0.00441

AC:

ExAC

AF:

0.00338

AC:

399

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SOX17: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.78

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.0097

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.46

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.011

Polyphen

0.81

Vest4

0.36

MVP

0.57

MPC

1.5

ClinPred

0.031

GERP RS

4.4

Varity_R

0.56

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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