13-36170783-T-C

Variant names:

• chr13-36170783-T-C
• rs76803829
• NM_017826.3:c.1005A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.00400

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=-0.83).
• 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 rank	MANE	Protein	UniProt
SOHLH2	NM_017826.3	c.1005A>G	p.Pro335Pro	synonymous_variant	Exon 10 of 11	ENST00000379881.8	NP_060296.2
CCDC169-SOHLH2	NM_001198910.2	c.1236A>G	p.Pro412Pro	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	c.1005A>G	p.Pro335Pro	synonymous_variant	Exon 10 of 11	1	NM_017826.3	ENSP00000369210.3
CCDC169-SOHLH2	ENST00000511166.1	c.1236A>G	p.Pro412Pro	synonymous_variant	Exon 15 of 16	2		ENSP00000421868.1

Frequencies

GnomAD3 genomes AF: 0.00801 AC: 1219 AN: 152206 Hom.: 9 Cov.: 32

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.: 3 AF XY: 0.00210 AC XY: 284 AN XY: 135398

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.: 11 Cov.: 32 AF XY: 0.00120 AC XY: 871 AN XY: 725550

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.: 9 Cov.: 32 AF XY: 0.00807 AC XY: 601 AN XY: 74490

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.: 2

Bravo AF: 0.00899

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SOHLH2-related disorder Benign:1

Mar 01, 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
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

Other links and lift over

dbSNP: rs76803829; hg19: chr13-36744920;