13-36202894-C-G

Variant names:

• chr13-36202894-C-G
• rs6563386
• NM_017826.3:c.49-801G>C

Variant summary

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

The NM_017826.3(SOHLH2):​c.49-801G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,092 control chromosomes in the GnomAD database, including 34,135 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 0.67 (34135 hom., cov: 32)
• Consequence: SOHLH2 NM_017826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH2	NM_017826.3	c.49-801G>C		intron_variant	Intron 1 of 10	ENST00000379881.8	NP_060296.2
CCDC169-SOHLH2	NM_001198910.2	c.280-801G>C		intron_variant	Intron 6 of 15		NP_001185839.1
SOHLH2	NM_001282147.2	c.49-801G>C		intron_variant	Intron 1 of 6		NP_001269076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOHLH2	ENST00000379881.8	c.49-801G>C		intron_variant	Intron 1 of 10	1	NM_017826.3	ENSP00000369210.3
CCDC169-SOHLH2	ENST00000511166.1	c.280-801G>C		intron_variant	Intron 6 of 15	2		ENSP00000421868.1
SOHLH2	ENST00000317764.6	c.49-801G>C		intron_variant	Intron 1 of 6	1		ENSP00000326838.6

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101417 AN: 151974 Hom.: 34101 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.667 AC: 101505 AN: 152092 Hom.: 34135 Cov.: 32 AF XY: 0.672 AC XY: 49989 AN XY: 74356

African (AFR) AF: 0.696 AC: 28883 AN: 41482

American (AMR) AF: 0.691 AC: 10556 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3468

East Asian (EAS) AF: 0.870 AC: 4494 AN: 5164

South Asian (SAS) AF: 0.710 AC: 3420 AN: 4816

European-Finnish (FIN) AF: 0.673 AC: 7134 AN: 10596

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42788 AN: 67966

Other (OTH) AF: 0.652 AC: 1378 AN: 2112

Alfa AF: 0.557 Hom.: 1723

Bravo AF: 0.670

Asia WGS AF: 0.807 AC: 2806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.70
PhyloP100		-0.99
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: rs6563386; hg19: chr13-36777031;