13-36189998-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

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. 14/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.724

Variant links:

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]

SOHLH2 links:

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]

CCDC169-SOHLH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06631744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH2	NM_017826.3 link	c.589G>A	p.Glu197Lys	missense_variant	Exon 6 of 11	ENST00000379881.8	NP_060296.2	Q9NX45-1
CCDC169-SOHLH2	NM_001198910.2 link	c.820G>A	p.Glu274Lys	missense_variant	Exon 11 of 16		NP_001185839.1
SOHLH2	NM_001282147.2 link	c.589G>A	p.Glu197Lys	missense_variant	Exon 6 of 7		NP_001269076.1	Q9NX45-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SOHLH2	ENST00000379881.8 link	c.589G>A	p.Glu197Lys	missense_variant	Exon 6 of 11	1	NM_017826.3	ENSP00000369210.3	Q9NX45-1
CCDC169-SOHLH2	ENST00000511166.1 link	c.820G>A	p.Glu274Lys	missense_variant	Exon 11 of 16	2		ENSP00000421868.1
SOHLH2	ENST00000317764.6 link	c.589G>A	p.Glu197Lys	missense_variant	Exon 6 of 7	1		ENSP00000326838.6	Q9NX45-2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

247920

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

134154

show subpopulations

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 SAS 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:

AN:

1454708

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

723516

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.820G>A (p.E274K) alteration is located in exon 11 (coding exon 10) of the CCDC169-SOHLH2 gene. This alteration results from a G to A substitution at nucleotide position 820, causing the glutamic acid (E) at amino acid position 274 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.6

L;L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.31

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.099

T;T;T

Sift4G

Benign

0.18

T;D;T

Polyphen

0.25

B;.;.

Vest4

0.17

MVP

0.27

MPC

0.31

ClinPred

0.18

GERP RS

4.2

Varity_R

0.041

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over