chr17-32996878-G-A

Position:

chr17-32996878-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173847.5(SPACA3):c.379G>A(p.Ala127Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,607,578 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.625

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:

SPACA3 (HGNC:):

SPACA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045260668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA3	NM_173847.5 linkuse as main transcript	c.379G>A	p.Ala127Thr	missense_variant	3/5	ENST00000269053.8	NP_776246.1	Q8IXA5-1A0A080YUZ7
SPACA3	NM_001317225.2 linkuse as main transcript	c.103G>A	p.Ala35Thr	missense_variant	3/5		NP_001304154.1	Q05C28
SPACA3	NM_001317226.2 linkuse as main transcript	c.70G>A	p.Ala24Thr	missense_variant	2/4		NP_001304155.1	Q8IXA5E9PF91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPACA3	ENST00000269053.8 linkuse as main transcript	c.379G>A	p.Ala127Thr	missense_variant	3/5	1	NM_173847.5	ENSP00000269053.3	Q8IXA5-1
SPACA3	ENST00000580599.5 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	4/6	1		ENSP00000463386.1	Q8IXA5-2
SPACA3	ENST00000394637.2 linkuse as main transcript	n.522G>A		non_coding_transcript_exon_variant	3/5	1
SPACA3	ENST00000394638.1 linkuse as main transcript	c.70G>A	p.Ala24Thr	missense_variant	2/4	3		ENSP00000378134.1	E9PF91

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

245856

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1455364

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723736

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000850

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

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

0.056

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.21

DEOGEN2

Benign

0.029

.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-3.9

.;N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

4.1

.;N;N

REVEL

Benign

0.19

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.26

MutPred

0.61

.;Gain of disorder (P = 0.1994);.;

MVP

0.19

MPC

0.073

ClinPred

0.037

GERP RS

0.98

Varity_R

0.054

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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