chr17-32995453-C-T

Variant names:

• chr17-32995453-C-T
• rs773677978
• ENST00000580599.5:c.-129C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001317225.2(SPACA3):​c.-220C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,612,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SPACA3 NM_001317225.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.39
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067919016).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317225.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA3	NM_173847.5	MANE Select	c.79C>T	p.Arg27Trp	missense	Exon 2 of 5	NP_776246.1	Q8IXA5-1
	SPACA3	NM_001317225.2		c.-220C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001304154.1	Q05C28
	SPACA3	NM_001317225.2		c.-220C>T		5_prime_UTR	Exon 2 of 5	NP_001304154.1	Q05C28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA3	ENST00000580599.5	TSL:1	c.-129C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	ENSP00000463386.1	Q8IXA5-2
	SPACA3	ENST00000269053.8	TSL:1 MANE Select	c.79C>T	p.Arg27Trp	missense	Exon 2 of 5	ENSP00000269053.3	Q8IXA5-1
	SPACA3	ENST00000580599.5	TSL:1	c.-129C>T		5_prime_UTR	Exon 3 of 6	ENSP00000463386.1	Q8IXA5-2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000402 AC: 10 AN: 248606 AF XY: 0.0000521

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1460352 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 726222

African (AFR) AF: 0.000149 AC: 5 AN: 33464

American (AMR) AF: 0.000112 AC: 5 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39666

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1110948

Other (OTH) AF: 0.0000331 AC: 2 AN: 60342

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74306

African (AFR) AF: 0.000193 AC: 8 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.097
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.027	D
Polyphen		0.48	P
Vest4		0.14
MVP		0.40
MPC		0.086
ClinPred		0.025	T
GERP RS		0.0055
Varity_R		0.050
gMVP		0.26
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs773677978; hg19: chr17-31322471;