Genetic Variant SPATA3:p.Gln96Arg (chr2-230996520-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_139073.5(SPATA3):c.287A>G(p.Gln96Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,551,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SPATA3
NM_139073.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.464

Publications

0 publications found

Variant links:

Genes affected

SPATA3 (HGNC:17884): (spermatogenesis associated 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA3 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

SPATA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059652627).

BP6

Variant 2-230996520-A-G is Benign according to our data. Variant chr2-230996520-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2608067.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA3	NM_139073.5 link	c.287A>G	p.Gln96Arg	missense_variant	Exon 1 of 5	ENST00000433428.7	NP_620712.2	Q8NHX4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA3	ENST00000433428.7 link	c.287A>G	p.Gln96Arg	missense_variant	Exon 1 of 5	1	NM_139073.5	ENSP00000403804.2		Q8NHX4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000108

AC:

AN:

156892

AF XY:

0.000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1399528

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

690244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25172

East Asian (EAS)

AF:

0.000588

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078956

Other (OTH)

AF:

0.0000689

AC:

AN:

58072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000387

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 29, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.94

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.00056

T;T;T;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.46

.;.;.;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0060

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

N;N;N;.;N;.

PhyloP100

-0.46

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.56

N;N;N;.;N;N

REVEL

Benign

0.050

Sift

Benign

0.96

T;T;T;.;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T

Vest4

0.019

MVP

0.040

ClinPred

0.014

GERP RS

0.55

PromoterAI

0.012

Neutral

(source)

Varity_R

0.025

gMVP

0.0087

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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2-230996520-A-G

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