Genetic Variant SOHLH1:p.Ala327Glu (chr9-135693781-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001101677.2(SOHLH1):c.980C>A(p.Ala327Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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. A327V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOHLH1
NM_001101677.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.240

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

SOHLH1 links:

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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=0.068039775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101677.2. 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
	SOHLH1	NM_001101677.2	MANE Select	c.980C>A	p.Ala327Glu	missense	Exon 8 of 8	NP_001095147.2	Q5JUK2-2
	SOHLH1	NM_001012415.3		c.*565C>A		3_prime_UTR	Exon 7 of 7	NP_001012415.3	Q5JUK2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOHLH1	ENST00000425225.2	TSL:5 MANE Select	c.980C>A	p.Ala327Glu	missense	Exon 8 of 8	ENSP00000404438.1	Q5JUK2-2
SOHLH1	ENST00000298466.9	TSL:1	c.*565C>A		3_prime_UTR	Exon 7 of 7	ENSP00000298466.5	Q5JUK2-1
SOHLH1	ENST00000950496.1		c.980C>A	p.Ala327Glu	missense	Exon 10 of 10	ENSP00000620555.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707470

African (AFR)

AF:

0.00

AC:

AN:

32598

American (AMR)

AF:

0.00

AC:

AN:

40734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25518

East Asian (EAS)

AF:

0.00

AC:

AN:

37556

South Asian (SAS)

AF:

0.00

AC:

AN:

81268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096026

Other (OTH)

AF:

0.00

AC:

AN:

59198

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.2

(source)

DANN

Benign

0.56

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.30

M_CAP

Benign

0.0027

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.0

PhyloP100

-0.24

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.69

REVEL

Benign

0.064

Sift

Uncertain

0.015

Sift4G

Benign

0.069

Polyphen

0.36

Vest4

0.18

MutPred

0.094

Loss of glycosylation at P330 (P = 0.1748)

MVP

0.16

MPC

0.046

ClinPred

0.081

GERP RS

-0.38

gMVP

0.027

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over