13-36170773-C-T

Position:

• chr13-36170773-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017826.3(SOHLH2):​c.1015G>A​(p.Ala339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,612,634 control chromosomes in the GnomAD database, including 42,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3562 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38796 hom.)
• Consequence: SOHLH2 NM_017826.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.309

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0795813E-4).
• BP6: Variant 13-36170773-C-T is Benign according to our data. Variant chr13-36170773-C-T is described in ClinVar as [Benign]. Clinvar id is 3059526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOHLH2	NM_017826.3	c.1015G>A	p.Ala339Thr	missense_variant	10/11	ENST00000379881.8
CCDC169-SOHLH2	NM_001198910.2	c.1246G>A	p.Ala416Thr	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOHLH2	ENST00000379881.8	c.1015G>A	p.Ala339Thr	missense_variant	10/11	1	NM_017826.3	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30304 AN: 151966 Hom.: 3556 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.244 AC: 61185 AN: 250750 Hom.: 8860 AF XY: 0.239 AC XY: 32383 AN XY: 135576

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.381

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.497

Gnomad SAS exome AF: 0.245

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.221 AC: 322664 AN: 1460550 Hom.: 38796 Cov.: 35 AF XY: 0.221 AC XY: 160371 AN XY: 726332

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.200 AC: 30342 AN: 152084 Hom.: 3562 Cov.: 32 AF XY: 0.200 AC XY: 14890 AN XY: 74342

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.172

Alfa AF: 0.204 Hom.: 8586

Bravo AF: 0.205

TwinsUK AF: 0.220 AC: 814

ALSPAC AF: 0.210 AC: 809

ESP6500AA AF: 0.150 AC: 663

ESP6500EA AF: 0.197 AC: 1693

ExAC AF: 0.237 AC: 28829

Asia WGS AF: 0.372 AC: 1294 AN: 3478

EpiCase AF: 0.198

EpiControl AF: 0.200

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SOHLH2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.14
DEOGEN2	Benign	0.069	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.33	T;T
MetaRNN	Benign	0.00011	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.3	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.20	N;N
REVEL	Benign	0.049
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.0080
MPC		0.21
ClinPred		0.00030	T
GERP RS		-3.6
Varity_R		0.022
gMVP		0.053

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: rs2296968; hg19: chr13-36744910;