Variant chr13-36189990-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017826.3(SOHLH2):c.597C>A(p.Asn199Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,454,346 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: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SOHLH2
NM_017826.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.478

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:):

CCDC169-SOHLH2 links:

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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=0.05799359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SOHLH2	NM_017826.3 linkuse as main transcript	c.597C>A	p.Asn199Lys	missense_variant	6/11	ENST00000379881.8
CCDC169-SOHLH2	NM_001198910.2 linkuse as main transcript	c.828C>A	p.Asn276Lys	missense_variant	11/16
SOHLH2	NM_001282147.2 linkuse as main transcript	c.597C>A	p.Asn199Lys	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOHLH2	ENST00000379881.8 linkuse as main transcript	c.597C>A	p.Asn199Lys	missense_variant	6/11	1	NM_017826.3	P1	Q9NX45-1
SOHLH2	ENST00000317764.6 linkuse as main transcript	c.597C>A	p.Asn199Lys	missense_variant	6/7	1			Q9NX45-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247938

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134134

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000963

AC:

AN:

1454346

Hom.:

Cov.:

AF XY:

0.00000968

AC XY:

AN XY:

723282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.828C>A (p.N276K) alteration is located in exon 11 (coding exon 10) of the CCDC169-SOHLH2 gene. This alteration results from a C to A substitution at nucleotide position 828, causing the asparagine (N) at amino acid position 276 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

0.22

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Uncertain

0.067

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.010

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.040

D;D;D

Sift4G

Benign

0.086

T;T;T

Polyphen

0.020

B;.;.

Vest4

0.18

MutPred

0.26

Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);.;

MVP

0.15

MPC

0.26

ClinPred

0.076

GERP RS

3.3

Varity_R

0.078

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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