Variant chr17-32996881-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_173847.5(SPACA3):c.382G>A(p.Ala128Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,608,768 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 87 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 91 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.12

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026901066).

BP6

Variant 17-32996881-G-A is Benign according to our data. Variant chr17-32996881-G-A is described in ClinVar as [Benign]. Clinvar id is 783778.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPACA3	NM_173847.5 linkuse as main transcript	c.382G>A	p.Ala128Thr	missense_variant	3/5	ENST00000269053.8
SPACA3	NM_001317225.2 linkuse as main transcript	c.106G>A	p.Ala36Thr	missense_variant	3/5
SPACA3	NM_001317226.2 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA3	ENST00000269053.8 linkuse as main transcript	c.382G>A	p.Ala128Thr	missense_variant	3/5	1	NM_173847.5	A2	Q8IXA5-1
SPACA3	ENST00000580599.5 linkuse as main transcript	c.175G>A	p.Ala59Thr	missense_variant	4/6	1		P2	Q8IXA5-2
SPACA3	ENST00000394637.2 linkuse as main transcript	n.525G>A		non_coding_transcript_exon_variant	3/5	1
SPACA3	ENST00000394638.1 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2883

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0611

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.000749

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.00529

AC:

1304

AN:

246624

Hom.:

AF XY:

0.00410

AC XY:

546

AN XY:

133222

show subpopulations

Gnomad AFR exome

AF:

0.0619

Gnomad AMR exome

AF:

0.00572

Gnomad ASJ exome

AF:

0.000813

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000715

Gnomad OTH exome

AF:

0.00470

GnomAD4 exome

AF:

0.00235

AC:

3420

AN:

1456436

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1525

AN XY:

724280

show subpopulations

Gnomad4 AFR exome

AF:

0.0634

Gnomad4 AMR exome

AF:

0.00672

Gnomad4 ASJ exome

AF:

0.000695

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000491

Gnomad4 OTH exome

AF:

0.00644

GnomAD4 genome

AF:

0.0190

AC:

2897

AN:

152332

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1395

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0613

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.0229

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0608

AC:

268

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00608

AC:

738

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.76

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.20

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

Sift4G

Benign

0.85

T;T;T

Polyphen

0.025

.;B;.

Vest4

0.33

MVP

0.39

MPC

0.16

ClinPred

0.00067

GERP RS

1.6

Varity_R

0.071

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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