13-36170769-G-A

Position:

chr13-36170769-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017826.3(SOHLH2):c.1019C>T(p.Ser340Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00025 in 1,613,578 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

SOHLH2
NM_017826.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06182185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOHLH2	NM_017826.3 link	c.1019C>T	p.Ser340Leu	missense_variant	10/11	ENST00000379881.8	NP_060296.2	Q9NX45-1
CCDC169-SOHLH2	NM_001198910.2 link	c.1250C>T	p.Ser417Leu	missense_variant	15/16		NP_001185839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOHLH2	ENST00000379881.8 link	c.1019C>T	p.Ser340Leu	missense_variant	10/11	1	NM_017826.3	ENSP00000369210.3		Q9NX45-1
CCDC169-SOHLH2	ENST00000511166.1 link	c.1250C>T	p.Ser417Leu	missense_variant	15/16	2		ENSP00000421868.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000219

AC:

AN:

250960

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000263

AC:

385

AN:

1461250

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

216

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000846

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000118

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000113

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2022

The c.1250C>T (p.S417L) alteration is located in exon 15 (coding exon 14) of the CCDC169-SOHLH2 gene. This alteration results from a C to T substitution at nucleotide position 1250, causing the serine (S) at amino acid position 417 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.99

D;.

Vest4

0.29

MVP

0.41

MPC

0.71

ClinPred

0.30

GERP RS

5.1

Varity_R

0.10

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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