Variant 17-32996978-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173847.5(SPACA3):c.479A>G(p.Asn160Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000286 in 1,575,760 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07

Variant links:

Genes affected

SPACA3 (HGNC:16260): (sperm acrosome associated 3) The protein encoded by this gene is a sperm surface protein that may be involved in adhesion to the egg prior to fertilization. While the encoded protein has significant similarity to lysozyme at the amino acid level, it has no detectable bacteriocidal activity. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

SPACA3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPACA3	NM_173847.5 linkuse as main transcript	c.479A>G	p.Asn160Ser	missense_variant	3/5	ENST00000269053.8
SPACA3	NM_001317225.2 linkuse as main transcript	c.203A>G	p.Asn68Ser	missense_variant	3/5
SPACA3	NM_001317226.2 linkuse as main transcript	c.170A>G	p.Asn57Ser	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA3	ENST00000269053.8 linkuse as main transcript	c.479A>G	p.Asn160Ser	missense_variant	3/5	1	NM_173847.5	A2	Q8IXA5-1
SPACA3	ENST00000580599.5 linkuse as main transcript	c.272A>G	p.Asn91Ser	missense_variant	4/6	1		P2	Q8IXA5-2
SPACA3	ENST00000394637.2 linkuse as main transcript	n.622A>G		non_coding_transcript_exon_variant	3/5	1
SPACA3	ENST00000394638.1 linkuse as main transcript	c.170A>G	p.Asn57Ser	missense_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

215948

Hom.:

AF XY:

0.0000519

AC XY:

AN XY:

115664

show subpopulations

Gnomad AFR exome

AF:

0.000265

Gnomad AMR exome

AF:

0.0000340

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000610

Gnomad SAS exome

AF:

0.000259

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1423432

Hom.:

Cov.:

AF XY:

0.0000255

AC XY:

AN XY:

705460

show subpopulations

Gnomad4 AFR exome

AF:

0.000342

Gnomad4 AMR exome

AF:

0.0000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000823

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000324

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.479A>G (p.N160S) alteration is located in exon 3 (coding exon 3) of the SPACA3 gene. This alteration results from a A to G substitution at nucleotide position 479, causing the asparagine (N) at amino acid position 160 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

T;T;T

M_CAP

Uncertain

0.090

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Uncertain

-0.25

MutationAssessor

Pathogenic

3.2

.;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.7

.;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.55

MVP

0.77

MPC

0.39

ClinPred

0.34

GERP RS

4.7

Varity_R

0.67

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over