13-36170583-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_017826.3(SOHLH2):c.1205G>A(p.Arg402Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,613,976 control chromosomes in the GnomAD database, including 348 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 Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R402W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.015 ( 26 hom., cov: 32)

Exomes 𝑓: 0.019 ( 322 hom. )

Consequence

SOHLH2
NM_017826.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.19

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:38866): (CCDC169-SOHLH2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C13orf38 (chromosome 13 open reading frame 38) and SOHLH2 (spermatogenesis and oogenesis specific basic helix-loop-helix 2) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

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=0.0019699037).

BP6

Variant 13-36170583-C-T is Benign according to our data. Variant chr13-36170583-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038235.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0146 (2218/152108) while in subpopulation NFE AF= 0.021 (1428/67996). AF 95% confidence interval is 0.0201. There are 26 homozygotes in gnomad4. There are 1099 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH2	NM_017826.3 link	c.1205G>A	p.Arg402Gln	missense_variant	Exon 10 of 11	ENST00000379881.8	NP_060296.2	Q9NX45-1
CCDC169-SOHLH2	NM_001198910.2 link	c.1436G>A	p.Arg479Gln	missense_variant	Exon 15 of 16		NP_001185839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOHLH2	ENST00000379881.8 link	c.1205G>A	p.Arg402Gln	missense_variant	Exon 10 of 11	1	NM_017826.3	ENSP00000369210.3		Q9NX45-1
CCDC169-SOHLH2	ENST00000511166.1 link	c.1436G>A	p.Arg479Gln	missense_variant	Exon 15 of 16	2		ENSP00000421868.1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2220

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00395

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0210

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0143

AC:

3599

AN:

251308

Hom.:

AF XY:

0.0145

AC XY:

1969

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.00590

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.0377

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.0187

AC:

27327

AN:

1461868

Hom.:

322

Cov.:

AF XY:

0.0184

AC XY:

13357

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.00639

Gnomad4 ASJ exome

AF:

0.00765

Gnomad4 EAS exome

AF:

0.00111

Gnomad4 SAS exome

AF:

0.00528

Gnomad4 FIN exome

AF:

0.0378

Gnomad4 NFE exome

AF:

0.0209

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0146

AC:

2218

AN:

152108

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1099

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00359

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.0370

Gnomad4 NFE

AF:

0.0210

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0180

Hom.:

Bravo

AF:

0.0122

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.0193

AC:

166

ExAC

AF:

0.0138

AC:

1674

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCDC169-SOHLH2-related disorder

Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

0.058

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.25

DEOGEN2

Benign

0.067

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.5

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

1.0

N;N

REVEL

Benign

0.047

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.026

MPC

0.24

ClinPred

0.0075

GERP RS

2.7

Varity_R

0.024

gMVP

0.044

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