13-36191833-G-A

Position:

• chr13-36191833-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_017826.3(SOHLH2):​c.492C>T​(p.Ser164Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00991 in 1,613,844 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (190 hom.)
• Consequence: SOHLH2 NM_017826.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0220

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 13-36191833-G-A is Benign according to our data. Variant chr13-36191833-G-A is described in ClinVar as [Benign]. Clinvar id is 3037375.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.022 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOHLH2	NM_017826.3	c.492C>T	p.Ser164Ser	synonymous_variant	5/11	ENST00000379881.8	NP_060296.2
CCDC169-SOHLH2	NM_001198910.2	c.723C>T	p.Ser241Ser	synonymous_variant	10/16		NP_001185839.1
SOHLH2	NM_001282147.2	c.492C>T	p.Ser164Ser	synonymous_variant	5/7		NP_001269076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOHLH2	ENST00000379881.8	c.492C>T	p.Ser164Ser	synonymous_variant	5/11	1	NM_017826.3	ENSP00000369210.3
CCDC169-SOHLH2	ENST00000511166.1	c.723C>T	p.Ser241Ser	synonymous_variant	10/16	2		ENSP00000421868.1
SOHLH2	ENST00000317764.6	c.492C>T	p.Ser164Ser	synonymous_variant	5/7	1		ENSP00000326838.6

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3583 AN: 152102 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0187

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00684

Gnomad OTH AF: 0.0205

GnomAD3 exomes AF: 0.0133 AC: 3352 AN: 251332 Hom.: 61 AF XY: 0.0132 AC XY: 1796 AN XY: 135830

Gnomad AFR exome AF: 0.0604

Gnomad AMR exome AF: 0.00766

Gnomad ASJ exome AF: 0.0358

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0223

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.00804

Gnomad OTH exome AF: 0.0139

GnomAD4 exome AF: 0.00849 AC: 12405 AN: 1461626 Hom.: 190 Cov.: 30 AF XY: 0.00889 AC XY: 6464 AN XY: 727116

Gnomad4 AFR exome AF: 0.0629

Gnomad4 AMR exome AF: 0.00888

Gnomad4 ASJ exome AF: 0.0340

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0215

Gnomad4 FIN exome AF: 0.00288

Gnomad4 NFE exome AF: 0.00533

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0236 AC: 3589 AN: 152218 Hom.: 84 Cov.: 32 AF XY: 0.0230 AC XY: 1711 AN XY: 74434

Gnomad4 AFR AF: 0.0630

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.00684

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0126 Hom.: 29

Bravo AF: 0.0254

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.0108

EpiControl AF: 0.0111

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SOHLH2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 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
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs9602419; hg19: chr13-36765970;