Variant chr13-36170773-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_017826.3(SOHLH2):c.1015G>A(p.Ala339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,612,634 control chromosomes in the GnomAD database, including 42,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3562 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38796 hom. )

Consequence

SOHLH2
NM_017826.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.309

Variant links:

Genes affected

SOHLH2 (HGNC:26026): (spermatogenesis and oogenesis specific basic helix-loop-helix 2) This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 13. The proteins encoded by this gene and another testis-specific transcription factor, SOHLH1, can form heterodimers, in addition to homodimers. There is a read-through locus (GeneID: 100526761) that shares sequence identity with this gene and the upstream CCDC169 (GeneID: 728591). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

SOHLH2 links:

CCDC169-SOHLH2 (HGNC:):

CCDC169-SOHLH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0795813E-4).

BP6

Variant 13-36170773-C-T is Benign according to our data. Variant chr13-36170773-C-T is described in ClinVar as [Benign]. Clinvar id is 3059526.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOHLH2	NM_017826.3 linkuse as main transcript	c.1015G>A	p.Ala339Thr	missense_variant	10/11	ENST00000379881.8
CCDC169-SOHLH2	NM_001198910.2 linkuse as main transcript	c.1246G>A	p.Ala416Thr	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOHLH2	ENST00000379881.8 linkuse as main transcript	c.1015G>A	p.Ala339Thr	missense_variant	10/11	1	NM_017826.3	P1	Q9NX45-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30304

AN:

151966

Hom.:

3556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.496

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.244

AC:

61185

AN:

250750

Hom.:

8860

AF XY:

0.239

AC XY:

32383

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.381

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.497

Gnomad SAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.221

AC:

322664

AN:

1460550

Hom.:

38796

Cov.:

AF XY:

0.221

AC XY:

160371

AN XY:

726332

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.503

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.200

AC:

30342

AN:

152084

Hom.:

3562

Cov.:

AF XY:

0.200

AC XY:

14890

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.281

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.495

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.204

Hom.:

8586

Bravo

AF:

0.205

TwinsUK

AF:

0.220

AC:

814

ALSPAC

AF:

0.210

AC:

809

ESP6500AA

AF:

0.150

AC:

663

ESP6500EA

AF:

0.197

AC:

1693

ExAC

AF:

0.237

AC:

28829

Asia WGS

AF:

0.372

AC:

1294

AN:

3478

EpiCase

AF:

0.198

EpiControl

AF:

0.200

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SOHLH2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.14

DEOGEN2

Benign

0.069

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.00011

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.3

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.049

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.0080

MPC

0.21

ClinPred

0.00030

GERP RS

-3.6

Varity_R

0.022

gMVP

0.053

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