9-135693644-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001101677.2(SOHLH1):c.1117C>G(p.Leu373Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,435,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SOHLH1
NM_001101677.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.447

Publications

0 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: 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=0.17494377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH1	NM_001101677.2 link	c.1117C>G	p.Leu373Val	missense_variant	Exon 8 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.1117C>G	p.Leu373Val	missense_variant	Exon 8 of 8	5	NM_001101677.2	ENSP00000404438.1	Q5JUK2-2
SOHLH1	ENST00000298466.9 link	c.*702C>G		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000298466.5	Q5JUK2-1
SOHLH1	ENST00000673731.1 link	c.541C>G	p.Leu181Val	missense_variant	Exon 5 of 5			ENSP00000501311.1	A0A669KBI8
SOHLH1	ENST00000674066.1 link	n.*16C>G		downstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000970

AC:

AN:

206112

AF XY:

0.00000898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1435178

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32810

American (AMR)

AF:

0.0000483

AC:

AN:

41382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25576

East Asian (EAS)

AF:

0.00

AC:

AN:

38028

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099276

Other (OTH)

AF:

0.00

AC:

AN:

59422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1117C>G (p.L373V) alteration is located in exon 8 (coding exon 8) of the SOHLH1 gene. This alteration results from a C to G substitution at nucleotide position 1117, causing the leucine (L) at amino acid position 373 to be replaced by a valine (V). 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

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.88

PhyloP100

0.45

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.87

Vest4

0.14

MutPred

0.30

Gain of methylation at K374 (P = 0.0436);

MVP

0.49

MPC

0.20

ClinPred

0.24

GERP RS

1.0

gMVP

0.021

Mutation Taster

=100/0

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.

9-135693644-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over