17-32996881-G-A

Position:

• chr17-32996881-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173847.5(SPACA3):​c.382G>A​(p.Ala128Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,608,768 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.019 (87 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (91 hom.)
• Consequence: SPACA3 NM_173847.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.12

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026901066).
• BP6: Variant 17-32996881-G-A is Benign according to our data. Variant chr17-32996881-G-A is described in ClinVar as [Benign]. Clinvar id is 783778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPACA3	NM_173847.5	c.382G>A	p.Ala128Thr	missense_variant	3/5	ENST00000269053.8
SPACA3	NM_001317225.2	c.106G>A	p.Ala36Thr	missense_variant	3/5
SPACA3	NM_001317226.2	c.73G>A	p.Ala25Thr	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA3	ENST00000269053.8	c.382G>A	p.Ala128Thr	missense_variant	3/5	1	NM_173847.5	A2
SPACA3	ENST00000580599.5	c.175G>A	p.Ala59Thr	missense_variant	4/6	1		P2
SPACA3	ENST00000394637.2	n.525G>A		non_coding_transcript_exon_variant	3/5	1
SPACA3	ENST00000394638.1	c.73G>A	p.Ala25Thr	missense_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2883 AN: 152214 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.000749

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.00529 AC: 1304 AN: 246624 Hom.: 39 AF XY: 0.00410 AC XY: 546 AN XY: 133222

Gnomad AFR exome AF: 0.0619

Gnomad AMR exome AF: 0.00572

Gnomad ASJ exome AF: 0.000813

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000135

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000715

Gnomad OTH exome AF: 0.00470

GnomAD4 exome AF: 0.00235 AC: 3420 AN: 1456436 Hom.: 91 Cov.: 31 AF XY: 0.00211 AC XY: 1525 AN XY: 724280

Gnomad4 AFR exome AF: 0.0634

Gnomad4 AMR exome AF: 0.00672

Gnomad4 ASJ exome AF: 0.000695

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000491

Gnomad4 OTH exome AF: 0.00644

GnomAD4 genome AF: 0.0190 AC: 2897 AN: 152332 Hom.: 87 Cov.: 33 AF XY: 0.0187 AC XY: 1395 AN XY: 74488

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00375 Hom.: 19

Bravo AF: 0.0229

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0608 AC: 268

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00608 AC: 738

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.76
DEOGEN2	Benign	0.0018	.;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.20	T;T;T
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.19	.;N;N
REVEL	Benign	0.092
Sift	Benign	0.74	.;T;T
Sift4G	Benign	0.85	T;T;T
Polyphen		0.025	.;B;.
Vest4		0.33
MVP		0.39
MPC		0.16
ClinPred		0.00067	T
GERP RS		1.6
Varity_R		0.071
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs35420663; hg19: chr17-31323899;