17-32995502-G-A

Position:

• chr17-32995502-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001317225.2(SPACA3):​c.-171G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: SPACA3 NM_001317225.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07940656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA3	NM_173847.5	c.128G>A	p.Ser43Asn	missense_variant	2/5	ENST00000269053.8	NP_776246.1
SPACA3	NM_001317225.2	c.-171G>A		5_prime_UTR_premature_start_codon_gain_variant	2/5		NP_001304154.1
SPACA3	NM_001317225.2	c.-171G>A		5_prime_UTR_variant	2/5		NP_001304154.1
SPACA3	NM_001317226.2	c.35-1341G>A		intron_variant			NP_001304155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA3	ENST00000269053.8	c.128G>A	p.Ser43Asn	missense_variant	2/5	1	NM_173847.5	ENSP00000269053.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.128G>A (p.S43N) alteration is located in exon 2 (coding exon 2) of the SPACA3 gene. This alteration results from a G to A substitution at nucleotide position 128, causing the serine (S) at amino acid position 43 to be replaced by an asparagine (N). 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	0.094
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.26	T
Polyphen		0.24	B
Vest4		0.10
MutPred		0.19		Loss of glycosylation at S43 (P = 0.0013);
MVP		0.62
MPC		0.12
ClinPred		0.21	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.051

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-31322520;