17-32996940-C-A

Variant names:

• chr17-32996940-C-A
• NM_173847.5:c.441C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_173847.5(SPACA3):​c.441C>A​(p.Ser147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SPACA3 NM_173847.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.570
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173847.5. 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.441C>A	p.Ser147Arg	missense	Exon 3 of 5	NP_776246.1	Q8IXA5-1
	SPACA3	NM_001317225.2		c.165C>A	p.Ser55Arg	missense	Exon 3 of 5	NP_001304154.1	Q05C28
	SPACA3	NM_001317226.2		c.132C>A	p.Ser44Arg	missense	Exon 2 of 4	NP_001304155.1	E9PF91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA3	ENST00000269053.8	TSL:1 MANE Select	c.441C>A	p.Ser147Arg	missense	Exon 3 of 5	ENSP00000269053.3	Q8IXA5-1
	SPACA3	ENST00000580599.5	TSL:1	c.234C>A	p.Ser78Arg	missense	Exon 4 of 6	ENSP00000463386.1	Q8IXA5-2
	SPACA3	ENST00000394637.2	TSL:1	n.584C>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	-0.067	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		0.57
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.93		Gain of MoRF binding (P = 0.053)
MVP		0.85
MPC		0.46
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.93
gMVP		0.83

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

Other links and lift over

hg19: chr17-31323958;