13-36170773-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.20 ( 3562 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38796 hom. )

Consequence

SOHLH2
NM_017826.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.309

Publications

29 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 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 VariationId is 3059526.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

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.1015G>A	p.Ala339Thr	missense	Exon 10 of 11	NP_060296.2	Q9NX45-1
	CCDC169-SOHLH2	NM_001198910.2		c.1246G>A	p.Ala416Thr	missense	Exon 15 of 16	NP_001185839.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH2	ENST00000379881.8	TSL:1 MANE Select	c.1015G>A	p.Ala339Thr	missense	Exon 10 of 11	ENSP00000369210.3	Q9NX45-1
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.1246G>A	p.Ala416Thr	missense	Exon 15 of 16	ENSP00000421868.1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30304

AN:

151966

Hom.:

3556

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.244

AC:

61185

AN:

250750

AF XY:

0.239

show subpopulations

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 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.:

AF XY:

0.221

AC XY:

160371

AN XY:

726332

show subpopulations

African (AFR)

AF:

0.139

AC:

4645

AN:

33436

American (AMR)

AF:

0.366

AC:

16373

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3645

AN:

26102

East Asian (EAS)

AF:

0.503

AC:

19947

AN:

39672

South Asian (SAS)

AF:

0.249

AC:

21449

AN:

86212

European-Finnish (FIN)

AF:

0.167

AC:

8906

AN:

53416

Middle Eastern (MID)

AF:

0.188

AC:

1079

AN:

5752

European-Non Finnish (NFE)

AF:

0.210

AC:

233680

AN:

1110928

Other (OTH)

AF:

0.214

AC:

12940

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

14243

28486

42730

56973

71216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8418

16836

25254

33672

42090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.200

AC:

30342

AN:

152084

Hom.:

3562

Cov.:

AF XY:

0.200

AC XY:

14890

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.142

AC:

5907

AN:

41496

American (AMR)

AF:

0.281

AC:

4286

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

467

AN:

3470

East Asian (EAS)

AF:

0.495

AC:

2557

AN:

5164

South Asian (SAS)

AF:

0.237

AC:

1141

AN:

4808

European-Finnish (FIN)

AF:

0.157

AC:

1662

AN:

10576

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13743

AN:

67988

Other (OTH)

AF:

0.172

AC:

364

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1195

2390

3585

4780

5975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.205

Hom.:

15718

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SOHLH2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.069

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.33

MetaRNN

Benign

0.00011

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.3

PhyloP100

-0.31

PrimateAI

Benign

0.34

PROVEAN

Benign

0.20

REVEL

Benign

0.049

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0080

MPC

0.21

ClinPred

0.00030

GERP RS

-3.6

Varity_R

0.022

gMVP

0.053

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over