Genetic Variant SPACA3:p.Pro21Leu (chr17-32995436-C-T) – 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>T(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,609,060 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SPACA3
NM_173847.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.205

Publications

1 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:

Genome browser will be placed here

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=0.082032114).

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>T	p.Pro21Leu	missense	Exon 2 of 5	NP_776246.1	Q8IXA5-1
SPACA3	NM_001317225.2		c.-237C>T		5_prime_UTR	Exon 2 of 5	NP_001304154.1	Q05C28
SPACA3	NM_001317226.2		c.35-1407C>T		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>T	p.Pro21Leu	missense	Exon 2 of 5	ENSP00000269053.3	Q8IXA5-1
SPACA3	ENST00000580599.5	TSL:1	c.-146C>T		5_prime_UTR	Exon 3 of 6	ENSP00000463386.1	Q8IXA5-2
SPACA3	ENST00000394637.2	TSL:1	n.183C>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

245648

AF XY:

0.0000226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456898

Hom.:

Cov.:

AF XY:

0.00000414

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:

0.000101

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:

0.00

AC:

AN:

1108994

Other (OTH)

AF:

0.00

AC:

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.60

M_CAP

Benign

0.013

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

PhyloP100

0.20

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.29

REVEL

Benign

0.14

Sift

Benign

0.53

Sift4G

Pathogenic

0.0

Polyphen

0.42

Vest4

0.11

MutPred

0.19

Gain of sheet (P = 0.0073)

MVP

0.63

MPC

0.31

ClinPred

0.41

GERP RS

4.1

Varity_R

0.052

gMVP

0.19

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over