13-36170783-T-C

Position:

chr13-36170783-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_017826.3(SOHLH2):c.1005A>G(p.Pro335Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,611,762 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0080 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 11 hom. )

Consequence

SOHLH2
NM_017826.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.00400

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=-0.83).

BP6

Variant 13-36170783-T-C is Benign according to our data. Variant chr13-36170783-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039034.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00801 (1220/152322) while in subpopulation AFR AF= 0.0243 (1012/41584). AF 95% confidence interval is 0.0231. There are 9 homozygotes in gnomad4. There are 601 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOHLH2	NM_017826.3 link	c.1005A>G	p.Pro335Pro	synonymous_variant	10/11	ENST00000379881.8	NP_060296.2	Q9NX45-1
CCDC169-SOHLH2	NM_001198910.2 link	c.1236A>G	p.Pro412Pro	synonymous_variant	15/16		NP_001185839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOHLH2	ENST00000379881.8 link	c.1005A>G	p.Pro335Pro	synonymous_variant	10/11	1	NM_017826.3	ENSP00000369210.3		Q9NX45-1
CCDC169-SOHLH2	ENST00000511166.1 link	c.1236A>G	p.Pro412Pro	synonymous_variant	15/16	2		ENSP00000421868.1

Frequencies

GnomAD3 genomes

AF:

0.00801

AC:

1219

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00264

AC:

661

AN:

250394

Hom.:

AF XY:

0.00210

AC XY:

284

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00921

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000725

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00128

AC:

1870

AN:

1459440

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

871

AN XY:

725550

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00882

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000422

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.00801

AC:

1220

AN:

152322

Hom.:

Cov.:

AF XY:

0.00807

AC XY:

601

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.00640

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00324

Hom.:

Bravo

AF:

0.00899

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SOHLH2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

DANN

Benign

0.44

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