17-32996940-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_173847.5(SPACA3):​c.441C>A​(p.Ser147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

SPACA3
NM_173847.5 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.570
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPACA3NM_173847.5 linkc.441C>A p.Ser147Arg missense_variant Exon 3 of 5 ENST00000269053.8 NP_776246.1 Q8IXA5-1A0A080YUZ7
SPACA3NM_001317225.2 linkc.165C>A p.Ser55Arg missense_variant Exon 3 of 5 NP_001304154.1 Q05C28
SPACA3NM_001317226.2 linkc.132C>A p.Ser44Arg missense_variant Exon 2 of 4 NP_001304155.1 Q8IXA5E9PF91

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPACA3ENST00000269053.8 linkc.441C>A p.Ser147Arg missense_variant Exon 3 of 5 1 NM_173847.5 ENSP00000269053.3 Q8IXA5-1
SPACA3ENST00000580599.5 linkc.234C>A p.Ser78Arg missense_variant Exon 4 of 6 1 ENSP00000463386.1 Q8IXA5-2
SPACA3ENST00000394637.2 linkn.584C>A non_coding_transcript_exon_variant Exon 3 of 5 1
SPACA3ENST00000394638.1 linkc.132C>A p.Ser44Arg missense_variant Exon 2 of 4 3 ENSP00000378134.1 E9PF91

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.441C>A (p.S147R) alteration is located in exon 3 (coding exon 3) of the SPACA3 gene. This alteration results from a C to A substitution at nucleotide position 441, causing the serine (S) at amino acid position 147 to be replaced by an arginine (R). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
.;T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Uncertain
-0.067
T
MutationAssessor
Pathogenic
3.5
.;H;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-4.8
.;D;D
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
.;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.87
MutPred
0.93
.;Gain of MoRF binding (P = 0.053);.;
MVP
0.85
MPC
0.46
ClinPred
1.0
D
GERP RS
3.7
Varity_R
0.93
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-31323958; API