9-135694417-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001101677.2(SOHLH1):c.916C>A(p.Leu306Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,613,312 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 36 hom. )

Consequence

SOHLH1
NM_001101677.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.11

Publications

6 publications found

Variant links:

Genes affected

SOHLH1 (HGNC:27845): (spermatogenesis and oogenesis specific basic helix-loop-helix 1) This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 9. Mutations in this gene are associated with nonobstructive azoospermia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

SOHLH1 Gene-Disease associations (from GenCC):

ovarian dysgenesis 5
Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
hypogonadism
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SOHLH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00800392).

BP6

Variant 9-135694417-G-T is Benign according to our data. Variant chr9-135694417-G-T is described in ClinVar as [Benign]. Clinvar id is 772940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH1	NM_001101677.2 link	c.916C>A	p.Leu306Met	missense_variant	Exon 7 of 8	ENST00000425225.2	NP_001095147.2	Q5JUK2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SOHLH1	ENST00000425225.2 link	c.916C>A	p.Leu306Met	missense_variant	Exon 7 of 8	5	NM_001101677.2	ENSP00000404438.1	Q5JUK2-2
SOHLH1	ENST00000298466.9 link	c.916C>A	p.Leu306Met	missense_variant	Exon 7 of 7	1		ENSP00000298466.5	Q5JUK2-1
SOHLH1	ENST00000673731.1 link	c.274C>A	p.Leu92Met	missense_variant	Exon 3 of 5			ENSP00000501311.1	A0A669KBI8
SOHLH1	ENST00000674066.1 link	n.2506C>A		non_coding_transcript_exon_variant	Exon 10 of 11

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

427

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00385

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00411

AC:

1025

AN:

249290

AF XY:

0.00495

show subpopulations

Gnomad AFR exome

AF:

0.000434

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00559

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000142

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00405

AC:

5913

AN:

1460992

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

3266

AN XY:

726778

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33478

American (AMR)

AF:

0.00255

AC:

114

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00551

AC:

144

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0143

AC:

1230

AN:

86254

European-Finnish (FIN)

AF:

0.000152

AC:

AN:

52576

Middle Eastern (MID)

AF:

0.00780

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00369

AC:

4101

AN:

1111988

Other (OTH)

AF:

0.00431

AC:

260

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

386

772

1157

1543

1929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00280

AC:

426

AN:

152320

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

217

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41568

American (AMR)

AF:

0.00261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0133

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00385

AC:

262

AN:

68034

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00321

Hom.:

Bravo

AF:

0.00265

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00399

AC:

484

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00510

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SOHLH1: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 19, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SOHLH1-related disorder

Benign:1

Apr 17, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.29

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L

PhyloP100

1.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

1.0

D;D

Vest4

0.30

MVP

0.77

MPC

0.24

ClinPred

0.048

GERP RS

3.2

Varity_R

0.15

gMVP

0.024

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

9-135694417-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over