13-36170653-C-G

Position:

• chr13-36170653-C-G

Variant summary

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

The NM_017826.3(SOHLH2):​c.1135G>C​(p.Ala379Pro) 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. 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)
• Consequence: SOHLH2 NM_017826.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00400

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:):

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=0.25568295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOHLH2	NM_017826.3	c.1135G>C	p.Ala379Pro	missense_variant	10/11	ENST00000379881.8
CCDC169-SOHLH2	NM_001198910.2	c.1366G>C	p.Ala456Pro	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOHLH2	ENST00000379881.8	c.1135G>C	p.Ala379Pro	missense_variant	10/11	1	NM_017826.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.1366G>C (p.A456P) alteration is located in exon 15 (coding exon 14) of the CCDC169-SOHLH2 gene. This alteration results from a G to C substitution at nucleotide position 1366, causing the alanine (A) at amino acid position 456 to be replaced by a proline (P). 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	0.24
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.98	D;.
Vest4		0.42
MutPred		0.24		Gain of disorder (P = 0.0528);.;
MVP		0.24
MPC		0.86
ClinPred		0.45	T
GERP RS		2.5
Varity_R		0.12
gMVP		0.41

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

Other links and lift over

dbSNP: rs1886938125; hg19: chr13-36744790;