Genetic Variant NM_139073.5:c.83C>T (chr2-230996316-C-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_139073.5(SPATA3):c.83C>T(p.Ser28Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)

Consequence

SPATA3
NM_139073.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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: 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=0.17451796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA3	NM_139073.5 link	c.83C>T	p.Ser28Phe	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.83C>T	p.Ser28Phe	missense_variant	Exon 1 of 5	1	NM_139073.5	ENSP00000403804.2		Q8NHX4

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150856

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000485

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73618

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41016

American (AMR)

AF:

0.00

AC:

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67572

Other (OTH)

AF:

0.000485

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.83C>T (p.S28F) alteration is located in exon 1 (coding exon 1) of the SPATA3 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the serine (S) at amino acid position 28 to be replaced by a phenylalanine (F). 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

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T;T;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.49

.;.;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;N;N;.;N

PhyloP100

1.7

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.4

D;D;D;.;D

REVEL

Benign

0.20

Sift

Uncertain

0.015

D;D;D;.;D

Sift4G

Uncertain

0.058

T;T;T;D;T

Vest4

0.17

MVP

0.14

ClinPred

0.65

GERP RS

4.0

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.16

gMVP

0.077

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over