17-32995472-T-A

Variant names:

• chr17-32995472-T-A
• rs2091716024
• NM_173847.5:c.98T>A

Variant summary

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

The NM_173847.5(SPACA3):​c.98T>A​(p.Leu33Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPACA3 NM_173847.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.324

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082111925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPACA3	NM_173847.5	c.98T>A	p.Leu33Gln	missense_variant	Exon 2 of 5	ENST00000269053.8	NP_776246.1
SPACA3	NM_001317225.2	c.-201T>A		5_prime_UTR_variant	Exon 2 of 5		NP_001304154.1
SPACA3	NM_001317226.2	c.35-1371T>A		intron_variant	Intron 1 of 3		NP_001304155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPACA3	ENST00000269053.8	c.98T>A	p.Leu33Gln	missense_variant	Exon 2 of 5	1	NM_173847.5	ENSP00000269053.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461372 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726874

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.98T>A (p.L33Q) alteration is located in exon 2 (coding exon 2) of the SPACA3 gene. This alteration results from a T to A substitution at nucleotide position 98, causing the leucine (L) at amino acid position 33 to be replaced by a glutamine (Q). 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	0.077
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.24
Sift	Benign	0.093	T
Sift4G	Benign	0.18	T
Polyphen		0.43	B
Vest4		0.30
MutPred		0.20		Loss of catalytic residue at L33 (P = 0.0058);
MVP		0.36
MPC		0.33
ClinPred		0.41	T
GERP RS		-0.25
Varity_R		0.11
gMVP		0.18

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

Other links and lift over

dbSNP: rs2091716024; hg19: chr17-31322490;