rs766883825

Variant names:

• chr17-32995462-G-C
• rs766883825
• ENST00000580599:c.-120G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-32995462-G-C
• chr17-32995462-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001317225.2(SPACA3):​c.-211G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPACA3 NM_001317225.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059384763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPACA3	NM_173847.5	c.88G>C	p.Val30Leu	missense_variant	Exon 2 of 5	ENST00000269053.8	NP_776246.1
SPACA3	NM_001317225.2	c.-211G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5		NP_001304154.1
SPACA3	NM_001317225.2	c.-211G>C		5_prime_UTR_variant	Exon 2 of 5		NP_001304154.1
SPACA3	NM_001317226.2	c.35-1381G>C		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.88G>C	p.Val30Leu	missense_variant	Exon 2 of 5	1	NM_173847.5	ENSP00000269053.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.0
DANN	Benign	0.53
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.12
Sift	Benign	0.52	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.033
MutPred		0.22		Loss of sheet (P = 0.0084);
MVP		0.34
MPC		0.074
ClinPred		0.11	T
GERP RS		-1.5
Varity_R		0.037
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766883825; hg19: chr17-31322480;