chr17-32997504-C-G

Position:

• chr17-32997504-C-G

Variant summary

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

The NM_173847.5(SPACA3):​c.562C>G​(p.Pro188Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P188L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPACA3 NM_173847.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPACA3	NM_173847.5	c.562C>G	p.Pro188Ala	missense_variant	4/5	ENST00000269053.8
SPACA3	NM_001317225.2	c.286C>G	p.Pro96Ala	missense_variant	4/5
SPACA3	NM_001317226.2	c.253C>G	p.Pro85Ala	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA3	ENST00000269053.8	c.562C>G	p.Pro188Ala	missense_variant	4/5	1	NM_173847.5	A2
SPACA3	ENST00000580599.5	c.355C>G	p.Pro119Ala	missense_variant	5/6	1		P2
SPACA3	ENST00000394637.2	n.705C>G		non_coding_transcript_exon_variant	4/5	1
SPACA3	ENST00000394638.1	c.253C>G	p.Pro85Ala	missense_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Mar 02, 2023

The c.562C>G (p.P188A) alteration is located in exon 4 (coding exon 4) of the SPACA3 gene. This alteration results from a C to G substitution at nucleotide position 562, causing the proline (P) at amino acid position 188 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.0092	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.034	.;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.3	.;M;.
MutationTaster	Benign	0.80	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	.;D;D
REVEL	Benign	0.23
Sift	Benign	0.077	.;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.081	.;B;.
Vest4		0.46
MutPred		0.44		.;Gain of helix (P = 0.1736);.;
MVP		0.79
MPC		0.11
ClinPred		0.32	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.46

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: chr17-31324522;