13-36189977-G-T

Variant names:

• chr13-36189977-G-T
• rs370201283
• NM_017826.3:c.610C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017826.3(SOHLH2):​c.610C>A​(p.Leu204Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,450,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. L204F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SOHLH2 NM_017826.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12932295).

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.610C>A	p.Leu204Ile	missense	Exon 6 of 11	NP_060296.2	Q9NX45-1
	CCDC169-SOHLH2	NM_001198910.2		c.841C>A	p.Leu281Ile	missense	Exon 11 of 16	NP_001185839.1
	SOHLH2	NM_001282147.2		c.610C>A	p.Leu204Ile	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.610C>A	p.Leu204Ile	missense	Exon 6 of 11	ENSP00000369210.3	Q9NX45-1
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.841C>A	p.Leu281Ile	missense	Exon 11 of 16	ENSP00000421868.1
	SOHLH2	ENST00000317764.6	TSL:1	c.610C>A	p.Leu204Ile	missense	Exon 6 of 7	ENSP00000326838.6	Q9NX45-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247800 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1450832 Hom.: 0 Cov.: 30 AF XY: 0.00000832 AC XY: 6 AN XY: 721494

African (AFR) AF: 0.00 AC: 0 AN: 33284

American (AMR) AF: 0.00 AC: 0 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 84448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.0000136 AC: 15 AN: 1105148

Other (OTH) AF: 0.00 AC: 0 AN: 59830

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	6.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.1	L
PhyloP100		-1.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.25
Sift	Benign	0.097	T
Sift4G	Uncertain	0.056	T
Polyphen		0.63	P
Vest4		0.18
MutPred		0.40		Gain of methylation at K201 (P = 0.0549)
MVP		0.28
MPC		0.26
ClinPred		0.088	T
GERP RS		2.1
Varity_R		0.052
gMVP		0.14
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: rs370201283; hg19: chr13-36764114;