Variant 17-32997505-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173847.5(SPACA3):c.563C>T(p.Pro188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,614,010 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P188A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.79

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008892834).

BP6

Variant 17-32997505-C-T is Benign according to our data. Variant chr17-32997505-C-T is described in ClinVar as [Benign]. Clinvar id is 725292.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPACA3	NM_173847.5 linkuse as main transcript	c.563C>T	p.Pro188Leu	missense_variant	4/5	ENST00000269053.8
SPACA3	NM_001317225.2 linkuse as main transcript	c.287C>T	p.Pro96Leu	missense_variant	4/5
SPACA3	NM_001317226.2 linkuse as main transcript	c.254C>T	p.Pro85Leu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA3	ENST00000269053.8 linkuse as main transcript	c.563C>T	p.Pro188Leu	missense_variant	4/5	1	NM_173847.5	A2	Q8IXA5-1
SPACA3	ENST00000580599.5 linkuse as main transcript	c.356C>T	p.Pro119Leu	missense_variant	5/6	1		P2	Q8IXA5-2
SPACA3	ENST00000394637.2 linkuse as main transcript	n.706C>T		non_coding_transcript_exon_variant	4/5	1
SPACA3	ENST00000394638.1 linkuse as main transcript	c.254C>T	p.Pro85Leu	missense_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

542

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00113

AC:

283

AN:

251448

Hom.:

AF XY:

0.000861

AC XY:

117

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000423

AC:

618

AN:

1461764

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

265

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00357

AC:

543

AN:

152246

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

245

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000822

Hom.:

Bravo

AF:

0.00401

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00132

AC:

160

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

-0.0097

Eigen_PC

Benign

-0.084

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

T;T;D

MetaRNN

Benign

0.0089

T;T;T

MetaSVM

Uncertain

-0.26

MutationTaster

Benign

0.91

D;D;D

PrimateAI

Benign

0.39

Sift4G

Uncertain

0.041

D;T;D

Polyphen

0.72

.;P;.

Vest4

0.62

MVP

0.84

MPC

0.44

ClinPred

0.12

GERP RS

4.4

Varity_R

0.23

gMVP

0.56

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

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