17-32995574-C-G

Variant summary

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

The NM_173847.5(SPACA3):ā€‹c.200C>Gā€‹(p.Ala67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 32)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.223
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]

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=0.048199713).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPACA3NM_173847.5 linkuse as main transcriptc.200C>G p.Ala67Gly missense_variant 2/5 ENST00000269053.8 NP_776246.1 Q8IXA5-1A0A080YUZ7
SPACA3NM_001317225.2 linkuse as main transcriptc.-99C>G 5_prime_UTR_variant 2/5 NP_001304154.1 Q05C28
SPACA3NM_001317226.2 linkuse as main transcriptc.35-1269C>G intron_variant NP_001304155.1 Q8IXA5E9PF91

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPACA3ENST00000269053.8 linkuse as main transcriptc.200C>G p.Ala67Gly missense_variant 2/51 NM_173847.5 ENSP00000269053.3 Q8IXA5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000716
AC:
18
AN:
251360
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000491
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:
0.000163
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000447
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:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000843
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000412
AC:
5

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 submitterclinical testingAmbry GeneticsAug 02, 2024The c.200C>G (p.A67G) alteration is located in exon 2 (coding exon 2) of the SPACA3 gene. This alteration results from a C to G substitution at nucleotide position 200, causing the alanine (A) at amino acid position 67 to be replaced by a glycine (G). 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
0.085
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
17
DANN
Uncertain
0.97
DEOGEN2
Benign
0.0036
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.069
Sift
Benign
0.12
T
Sift4G
Benign
0.23
T
Polyphen
0.14
B
Vest4
0.19
MutPred
0.22
Loss of helix (P = 0.079);
MVP
0.46
MPC
0.086
ClinPred
0.024
T
GERP RS
2.6
Varity_R
0.057
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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.

Other links and lift over

dbSNP: rs751713020; hg19: chr17-31322592; API