Genetic Variant SOHLH2:p.Tyr375Tyr (chr13-36170663-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_017826.3(SOHLH2):c.1125C>T(p.Tyr375Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,614,114 control chromosomes in the GnomAD database, including 10,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.086 ( 745 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9619 hom. )

Consequence

SOHLH2
NM_017826.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.220

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 13-36170663-G-A is Benign according to our data. Variant chr13-36170663-G-A is described in ClinVar as [Benign]. Clinvar id is 3056894.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH2	NM_017826.3 link	c.1125C>T	p.Tyr375Tyr	synonymous_variant	Exon 10 of 11	ENST00000379881.8	NP_060296.2	Q9NX45-1
CCDC169-SOHLH2	NM_001198910.2 link	c.1356C>T	p.Tyr452Tyr	synonymous_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.1125C>T	p.Tyr375Tyr	synonymous_variant	Exon 10 of 11	1	NM_017826.3	ENSP00000369210.3		Q9NX45-1
CCDC169-SOHLH2	ENST00000511166.1 link	c.1356C>T	p.Tyr452Tyr	synonymous_variant	Exon 15 of 16	2		ENSP00000421868.1

Frequencies

GnomAD3 genomes

AF:

0.0859

AC:

13067

AN:

152110

Hom.:

744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0865

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0728

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0923

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.103

AC:

25921

AN:

251344

Hom.:

1549

AF XY:

0.108

AC XY:

14660

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.0617

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.0819

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0877

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.112

AC:

163562

AN:

1461886

Hom.:

9619

Cov.:

AF XY:

0.113

AC XY:

82364

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.0648

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.0701

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0890

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0858

AC:

13067

AN:

152228

Hom.:

745

Cov.:

AF XY:

0.0858

AC XY:

6389

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.0862

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.0726

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0923

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.118

Hom.:

1885

Bravo

AF:

0.0838

Asia WGS

AF:

0.0880

AC:

308

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCDC169-SOHLH2-related disorder

Benign:1

Nov 08, 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

-0.87

CADD

Benign

5.5

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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