rs9593921

Variant names:

• chr13-36206363-A-C
• rs9593921
• NM_017826.3:c.49-4270T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_017826.3(SOHLH2):​c.49-4270T>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
• Publications: 2 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=-0.64).
• 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 rank	MANE	Protein	UniProt
SOHLH2	NM_017826.3	c.49-4270T>G		intron_variant	Intron 1 of 10	ENST00000379881.8	NP_060296.2
CCDC169-SOHLH2	NM_001198910.2	c.280-4270T>G		intron_variant	Intron 6 of 15		NP_001185839.1
SOHLH2	NM_001282147.2	c.49-4270T>G		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.49-4270T>G		intron_variant	Intron 1 of 10	1	NM_017826.3	ENSP00000369210.3
CCDC169-SOHLH2	ENST00000511166.1	c.280-4270T>G		intron_variant	Intron 6 of 15	2		ENSP00000421868.1
SOHLH2	ENST00000317764.6	c.49-4270T>G		intron_variant	Intron 1 of 6	1		ENSP00000326838.6

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

African (AFR) AF: 0.0584 AC: 2423 AN: 41524

American (AMR) AF: 0.0103 AC: 157 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0186 AC: 90 AN: 4832

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00702 AC: 477 AN: 67904

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0121 Hom.: 36

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
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

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: rs9593921; hg19: chr13-36780500;