dbSNP rs777430082: SPACA1:p.Thr33Ser (chr6-88048003-C-G) – 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_030960.3(SPACA1):c.98C>G(p.Thr33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,432,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. T33I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPACA1
NM_030960.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.24

Publications

0 publications found

Variant links:

Genes affected

SPACA1 (HGNC:14967): (sperm acrosome associated 1) The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm antibodies from infertile males. Furthermore, antibodies generated against the recombinant protein block in vitro fertilization. This protein localizes to the acrosomal membrane of spermatids and mature spermatozoa where it is thought to play a role in acrosomal morphogenesis and in sperm-egg binding and fusion, respectively. [provided by RefSeq, Jul 2008]

SPACA1 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=0.18982884).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030960.3. 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
	SPACA1	NM_030960.3	MANE Select	c.98C>G	p.Thr33Ser	missense	Exon 1 of 7	NP_112222.1	Q9HBV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA1	ENST00000237201.2	TSL:1 MANE Select	c.98C>G	p.Thr33Ser	missense	Exon 1 of 7	ENSP00000237201.1	Q9HBV2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1432828

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709580

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33256

American (AMR)

AF:

0.00

AC:

AN:

38718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25428

East Asian (EAS)

AF:

0.00

AC:

AN:

38674

South Asian (SAS)

AF:

0.00

AC:

AN:

81546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099846

Other (OTH)

AF:

0.00

AC:

AN:

59438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

0.19

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.37

M_CAP

Benign

0.0064

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

3.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.7

REVEL

Benign

0.086

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.59

Vest4

0.18

MutPred

0.17

Loss of glycosylation at T33 (P = 0.042)

MVP

0.34

MPC

1.3

ClinPred

0.89

GERP RS

3.8

PromoterAI

-0.062

Neutral

(source)

Varity_R

0.16

gMVP

0.70

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over