17-32996854-G-A

Position:

• chr17-32996854-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173847.5(SPACA3):​c.355G>A​(p.Ala119Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,445,570 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPACA3 NM_173847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPACA3	NM_173847.5	c.355G>A	p.Ala119Thr	missense_variant	3/5	ENST00000269053.8
SPACA3	NM_001317225.2	c.79G>A	p.Ala27Thr	missense_variant	3/5
SPACA3	NM_001317226.2	c.46G>A	p.Ala16Thr	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA3	ENST00000269053.8	c.355G>A	p.Ala119Thr	missense_variant	3/5	1	NM_173847.5	A2
SPACA3	ENST00000580599.5	c.148G>A	p.Ala50Thr	missense_variant	4/6	1		P2
SPACA3	ENST00000394637.2	n.498G>A		non_coding_transcript_exon_variant	3/5	1
SPACA3	ENST00000394638.1	c.46G>A	p.Ala16Thr	missense_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000843 AC: 2 AN: 237254 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 127746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000612

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: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445570 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000464

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: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Pathogenic	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.50	D
MutationTaster	Benign	0.90	D;D;D
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	0.068	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.71
MutPred		0.82		.;Loss of sheet (P = 0.1501);.;
MVP		0.88
MPC		0.43
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.58
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1370162190; hg19: chr17-31323872;