13-36196880-C-T

Variant names:

• chr13-36196880-C-T
• rs7327064
• NM_017826.3:c.264-3013G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017826.3(SOHLH2):​c.264-3013G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,104 control chromosomes in the GnomAD database, including 3,057 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3057 hom., cov: 32)
• Consequence: SOHLH2 NM_017826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 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.264-3013G>A		intron	N/A	NP_060296.2	Q9NX45-1
	CCDC169-SOHLH2	NM_001198910.2		c.495-3013G>A		intron	N/A	NP_001185839.1
	SOHLH2	NM_001282147.2		c.264-3013G>A		intron	N/A	NP_001269076.1	Q9NX45-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH2	ENST00000379881.8	TSL:1 MANE Select	c.264-3013G>A		intron	N/A	ENSP00000369210.3	Q9NX45-1
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.495-3013G>A		intron	N/A	ENSP00000421868.1
	SOHLH2	ENST00000317764.6	TSL:1	c.264-3013G>A		intron	N/A	ENSP00000326838.6	Q9NX45-2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29093 AN: 151986 Hom.: 3057 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29100 AN: 152104 Hom.: 3057 Cov.: 32 AF XY: 0.189 AC XY: 14056 AN XY: 74340

African (AFR) AF: 0.132 AC: 5462 AN: 41508

American (AMR) AF: 0.212 AC: 3231 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3468

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5158

South Asian (SAS) AF: 0.158 AC: 763 AN: 4826

European-Finnish (FIN) AF: 0.224 AC: 2370 AN: 10576

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15845 AN: 67986

Other (OTH) AF: 0.204 AC: 430 AN: 2104

Alfa AF: 0.211 Hom.: 9705

Bravo AF: 0.187

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.50
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7327064; hg19: chr13-36771017;