rs9593921

Positions:

• chr13-36206363-A-C
• chr13-36206363-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017826.3(SOHLH2):​c.49-4270T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,106 control chromosomes in the GnomAD database, including 65 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 0.022 (65 hom., cov: 32)
• Consequence: SOHLH2 NM_017826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOHLH2	NM_017826.3	c.49-4270T>G		intron_variant		ENST00000379881.8	NP_060296.2
CCDC169-SOHLH2	NM_001198910.2	c.280-4270T>G		intron_variant			NP_001185839.1
SOHLH2	NM_001282147.2	c.49-4270T>G		intron_variant			NP_001269076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOHLH2	ENST00000379881.8	c.49-4270T>G		intron_variant		1	NM_017826.3	ENSP00000369210	P1
SOHLH2	ENST00000317764.6	c.49-4270T>G		intron_variant		1		ENSP00000326838

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3397 AN: 151988 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00702

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0224 AC: 3401 AN: 152106 Hom.: 65 Cov.: 32 AF XY: 0.0218 AC XY: 1620 AN XY: 74368

Gnomad4 AFR AF: 0.0584

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.00702

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0100 Hom.: 17

Bravo AF: 0.0240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.8
DANN	Benign	0.78

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: rs9593921; hg19: chr13-36780500;