Genetic Variant SPATA3:p.Asp88Asn (chr2-230996495-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_139073.5(SPATA3):c.262G>A(p.Asp88Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,552,174 control chromosomes in the GnomAD database, including 46 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 43 hom. )

Consequence

SPATA3
NM_139073.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.397

Publications

8 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044586062).

BP6

Variant 2-230996495-G-A is Benign according to our data. Variant chr2-230996495-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651993.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA3	NM_139073.5 link	c.262G>A	p.Asp88Asn	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.262G>A	p.Asp88Asn	missense_variant	Exon 1 of 5	1	NM_139073.5	ENSP00000403804.2		Q8NHX4

Frequencies

GnomAD3 genomes

AF:

0.00428

AC:

652

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00735

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00343

AC:

541

AN:

157788

AF XY:

0.00350

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00200

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000765

Gnomad NFE exome

AF:

0.00678

Gnomad OTH exome

AF:

0.00335

GnomAD4 exome

AF:

0.00648

AC:

9070

AN:

1399856

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

4369

AN XY:

690402

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

31598

American (AMR)

AF:

0.00185

AC:

AN:

35708

Ashkenazi Jewish (ASJ)

AF:

0.00274

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35740

South Asian (SAS)

AF:

0.00202

AC:

160

AN:

79236

European-Finnish (FIN)

AF:

0.000586

AC:

AN:

49484

Middle Eastern (MID)

AF:

0.00298

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00780

AC:

8414

AN:

1079064

Other (OTH)

AF:

0.00487

AC:

283

AN:

58140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

601

1202

1802

2403

3004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00427

AC:

651

AN:

152318

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41570

American (AMR)

AF:

0.00346

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00735

AC:

500

AN:

68030

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00578

Hom.:

Bravo

AF:

0.00414

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00691

AC:

ExAC

AF:

0.00274

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SPATA3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.84

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0032

T;T;T;.;T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.40

.;.;.;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0045

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;L;.;L;.

PhyloP100

-0.40

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

N;N;N;.;N;D

REVEL

Benign

0.013

Sift

Benign

0.14

T;T;T;.;T;.

Sift4G

Uncertain

0.026

D;D;D;D;D;D

Vest4

0.091

MVP

0.092

ClinPred

0.0010

GERP RS

-1.8

PromoterAI

0.0022

Neutral

(source)

Varity_R

0.033

gMVP

0.024

Mutation Taster

=100/0

polymorphism

(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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chr2-230996495-G-A

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