13-36170892-C-T

Variant names:

• chr13-36170892-C-T
• rs1328641
• NM_017826.3:c.1001-105G>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.1001-105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,498,676 control chromosomes in the GnomAD database, including 57,992 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 0.25 (5059 hom., cov: 33)
  • Exomes 𝑓: 0.28 (52933 hom.)
• Consequence: SOHLH2 NM_017826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.281 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.1001-105G>A		intron	N/A	NP_060296.2	Q9NX45-1
	CCDC169-SOHLH2	NM_001198910.2		c.1232-105G>A		intron	N/A	NP_001185839.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH2	ENST00000379881.8	TSL:1 MANE Select	c.1001-105G>A		intron	N/A	ENSP00000369210.3	Q9NX45-1
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.1232-105G>A		intron	N/A	ENSP00000421868.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37848 AN: 151970 Hom.: 5057 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.278 AC: 374182 AN: 1346588 Hom.: 52933 AF XY: 0.279 AC XY: 184390 AN XY: 661438

African (AFR) AF: 0.154 AC: 4604 AN: 29840

American (AMR) AF: 0.216 AC: 6875 AN: 31818

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 5439 AN: 20502

East Asian (EAS) AF: 0.239 AC: 8965 AN: 37444

South Asian (SAS) AF: 0.283 AC: 19798 AN: 69842

European-Finnish (FIN) AF: 0.363 AC: 16104 AN: 44308

Middle Eastern (MID) AF: 0.257 AC: 1366 AN: 5324

European-Non Finnish (NFE) AF: 0.281 AC: 295646 AN: 1051748

Other (OTH) AF: 0.276 AC: 15385 AN: 55762

GnomAD4 genome AF: 0.249 AC: 37848 AN: 152088 Hom.: 5059 Cov.: 33 AF XY: 0.253 AC XY: 18825 AN XY: 74326

African (AFR) AF: 0.160 AC: 6622 AN: 41510

American (AMR) AF: 0.232 AC: 3552 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3466

East Asian (EAS) AF: 0.220 AC: 1137 AN: 5166

South Asian (SAS) AF: 0.294 AC: 1418 AN: 4826

European-Finnish (FIN) AF: 0.383 AC: 4033 AN: 10534

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19253 AN: 67980

Other (OTH) AF: 0.254 AC: 537 AN: 2112

Alfa AF: 0.266 Hom.: 5821

Bravo AF: 0.232

Asia WGS AF: 0.258 AC: 897 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	1.8
DANN	Benign	0.73
PhyloP100		-0.17
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: rs1328641; hg19: chr13-36745029; COSMIC: COSV107492543;