NM_017826.3:c.1125C>T

Variant names:

• chr13-36170663-G-A
• rs2296967
• NM_017826.3:c.1125C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.220
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017826.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH2	NM_017826.3	MANE Select	c.1125C>T	p.Tyr375Tyr	synonymous	Exon 10 of 11	NP_060296.2	Q9NX45-1
	CCDC169-SOHLH2	NM_001198910.2		c.1356C>T	p.Tyr452Tyr	synonymous	Exon 15 of 16	NP_001185839.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH2	ENST00000379881.8	TSL:1 MANE Select	c.1125C>T	p.Tyr375Tyr	synonymous	Exon 10 of 11	ENSP00000369210.3	Q9NX45-1
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.1356C>T	p.Tyr452Tyr	synonymous	Exon 15 of 16	ENSP00000421868.1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13067 AN: 152110 Hom.: 744 Cov.: 32

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

GnomAD2 exomes AF: 0.103 AC: 25921 AN: 251344 AF XY: 0.108

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 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.: 32 AF XY: 0.113 AC XY: 82364 AN XY: 727242

African (AFR) AF: 0.0188 AC: 628 AN: 33480

American (AMR) AF: 0.0648 AC: 2899 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5182 AN: 26136

East Asian (EAS) AF: 0.0701 AC: 2781 AN: 39700

South Asian (SAS) AF: 0.126 AC: 10871 AN: 86258

European-Finnish (FIN) AF: 0.0890 AC: 4754 AN: 53420

Middle Eastern (MID) AF: 0.146 AC: 843 AN: 5768

European-Non Finnish (NFE) AF: 0.116 AC: 129009 AN: 1112004

Other (OTH) AF: 0.109 AC: 6595 AN: 60396

GnomAD4 genome AF: 0.0858 AC: 13067 AN: 152228 Hom.: 745 Cov.: 32 AF XY: 0.0858 AC XY: 6389 AN XY: 74434

African (AFR) AF: 0.0220 AC: 916 AN: 41550

American (AMR) AF: 0.0862 AC: 1319 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3470

East Asian (EAS) AF: 0.0726 AC: 376 AN: 5182

South Asian (SAS) AF: 0.123 AC: 594 AN: 4816

European-Finnish (FIN) AF: 0.0923 AC: 978 AN: 10600

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7911 AN: 67998

Other (OTH) AF: 0.115 AC: 242 AN: 2112

Alfa AF: 0.115 Hom.: 2270

Bravo AF: 0.0838

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CCDC169-SOHLH2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.30
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2296967; hg19: chr13-36744800; COSMIC: COSV65901225;