rs755193720

Variant names:

• chr13-36189998-C-G
• rs755193720
• NM_017826.3:c.589G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-36189998-C-G
• chr13-36189998-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017826.3(SOHLH2):​c.589G>C​(p.Glu197Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E197K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOHLH2 NM_017826.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12641406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH2	NM_017826.3	c.589G>C	p.Glu197Gln	missense_variant	Exon 6 of 11	ENST00000379881.8	NP_060296.2
CCDC169-SOHLH2	NM_001198910.2	c.820G>C	p.Glu274Gln	missense_variant	Exon 11 of 16		NP_001185839.1
SOHLH2	NM_001282147.2	c.589G>C	p.Glu197Gln	missense_variant	Exon 6 of 7		NP_001269076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOHLH2	ENST00000379881.8	c.589G>C	p.Glu197Gln	missense_variant	Exon 6 of 11	1	NM_017826.3	ENSP00000369210.3
CCDC169-SOHLH2	ENST00000511166.1	c.820G>C	p.Glu274Gln	missense_variant	Exon 11 of 16	2		ENSP00000421868.1
SOHLH2	ENST00000317764.6	c.589G>C	p.Glu197Gln	missense_variant	Exon 6 of 7	1		ENSP00000326838.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.97	D;.;.
Vest4		0.12
MutPred		0.13		Loss of ubiquitination at K200 (P = 0.0246);Loss of ubiquitination at K200 (P = 0.0246);.;
MVP		0.43
MPC		0.75
ClinPred		0.82	D
GERP RS		4.2
Varity_R		0.073
gMVP		0.31

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: rs755193720; hg19: chr13-36764135;