rs755193720

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017826.3(SOHLH2):​c.589G>A​(p.Glu197Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,606,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SOHLH2 NM_017826.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.724
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06631744).
• BS2: High AC in GnomAd4 at 10 AD gene.

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.589G>A	p.Glu197Lys	missense	Exon 6 of 11	NP_060296.2	Q9NX45-1
	CCDC169-SOHLH2	NM_001198910.2		c.820G>A	p.Glu274Lys	missense	Exon 11 of 16	NP_001185839.1
	SOHLH2	NM_001282147.2		c.589G>A	p.Glu197Lys	missense	Exon 6 of 7	NP_001269076.1	Q9NX45-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH2	ENST00000379881.8	TSL:1 MANE Select	c.589G>A	p.Glu197Lys	missense	Exon 6 of 11	ENSP00000369210.3	Q9NX45-1
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.820G>A	p.Glu274Lys	missense	Exon 11 of 16	ENSP00000421868.1
	SOHLH2	ENST00000317764.6	TSL:1	c.589G>A	p.Glu197Lys	missense	Exon 6 of 7	ENSP00000326838.6	Q9NX45-2

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 247920 AF XY: 0.0000224

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1454708 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 723516

African (AFR) AF: 0.000150 AC: 5 AN: 33256

American (AMR) AF: 0.0000452 AC: 2 AN: 44288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.00 AC: 0 AN: 85052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1107854

Other (OTH) AF: 0.0000167 AC: 1 AN: 60044

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74284

African (AFR) AF: 0.000145 AC: 6 AN: 41404

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.066	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.6	L
PhyloP100		0.72
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.12
Sift	Benign	0.099	T
Sift4G	Benign	0.18	T
Polyphen		0.25	B
Vest4		0.17
MVP		0.27
MPC		0.31
ClinPred		0.18	T
GERP RS		4.2
Varity_R		0.041
gMVP		0.40
Mutation Taster		=95/5	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: rs755193720; hg19: chr13-36764135; COSMIC: COSV58523222;