dbSNP rs1228488994: SPACA3:p.Pro21His (chr17-32995436-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173847.5(SPACA3):c.62C>A(p.Pro21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P21L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.205

Publications

0 publications found

Variant links:

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]

SPACA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18105555).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPACA3	NM_173847.5	MANE Select	c.62C>A	p.Pro21His	missense	Exon 2 of 5	NP_776246.1	Q8IXA5-1
SPACA3	NM_001317225.2		c.-237C>A		5_prime_UTR	Exon 2 of 5	NP_001304154.1	Q05C28
SPACA3	NM_001317226.2		c.35-1407C>A		intron	N/A	NP_001304155.1	E9PF91

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPACA3	ENST00000269053.8	TSL:1 MANE Select	c.62C>A	p.Pro21His	missense	Exon 2 of 5	ENSP00000269053.3	Q8IXA5-1
SPACA3	ENST00000580599.5	TSL:1	c.-146C>A		5_prime_UTR	Exon 3 of 6	ENSP00000463386.1	Q8IXA5-2
SPACA3	ENST00000394637.2	TSL:1	n.183C>A		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456898

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25714

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

85474

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1108994

Other (OTH)

AF:

0.00

AC:

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0060

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.42

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.8

PhyloP100

0.20

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.50

REVEL

Benign

0.23

Sift

Uncertain

0.013

Sift4G

Pathogenic

0.0

Polyphen

0.94

Vest4

0.19

MutPred

0.17

Loss of glycosylation at P21 (P = 0.0273)

MVP

0.75

MPC

0.41

ClinPred

0.76

GERP RS

4.1

Varity_R

0.091

gMVP

0.21

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over