Variant 17-32996854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173847.5(SPACA3):c.355G>A(p.Ala119Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,445,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPACA3	NM_173847.5 linkuse as main transcript	c.355G>A	p.Ala119Thr	missense_variant	3/5	ENST00000269053.8
SPACA3	NM_001317225.2 linkuse as main transcript	c.79G>A	p.Ala27Thr	missense_variant	3/5
SPACA3	NM_001317226.2 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA3	ENST00000269053.8 linkuse as main transcript	c.355G>A	p.Ala119Thr	missense_variant	3/5	1	NM_173847.5	A2	Q8IXA5-1
SPACA3	ENST00000580599.5 linkuse as main transcript	c.148G>A	p.Ala50Thr	missense_variant	4/6	1		P2	Q8IXA5-2
SPACA3	ENST00000394637.2 linkuse as main transcript	n.498G>A		non_coding_transcript_exon_variant	3/5	1
SPACA3	ENST00000394638.1 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000843

AC:

AN:

237254

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000612

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445570

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000464

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 20, 2024

The c.355G>A (p.A119T) alteration is located in exon 3 (coding exon 3) of the SPACA3 gene. This alteration results from a G to A substitution at nucleotide position 355, causing the alanine (A) at amino acid position 119 to be replaced by a threonine (T). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

.;T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Uncertain

0.50

MutationAssessor

Uncertain

2.5

.;M;.

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.6

.;D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.022

.;D;D

Sift4G

Benign

0.068

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.71

MutPred

0.82

.;Loss of sheet (P = 0.1501);.;

MVP

0.88

MPC

0.43

ClinPred

0.99

GERP RS

4.6

Varity_R

0.58

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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