Genetic Variant SPA17:p.Asn71Ser (chr11-124681446-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017425.4(SPA17):c.212A>G(p.Asn71Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,431,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SPA17
NM_017425.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

Variant links:

Genes affected

SPA17 (HGNC:11210): (sperm autoantigenic protein 17) This gene encodes a protein present at the cell surface. The N-terminus has sequence similarity to human cAMP-dependent protein kinase A (PKA) type II alpha regulatory subunit (RIIa) while the C-terminus has an IQ calmodulin-binding motif. The central portion of the protein has carbohydrate binding motifs and likely functions in cell-cell adhesion. The protein was initially characterized by its involvement in the binding of sperm to the zona pellucida of the oocyte. Recent studies indicate that it is also involved in additional cell-cell adhesion functions such as immune cell migration and metastasis. A retrotransposed pseudogene is present on chromosome 10q22.[provided by RefSeq, Jan 2009]

SPA17 links:

SIAE (HGNC:18187): (sialic acid acetylesterase) This gene encodes an enzyme which removes 9-O-acetylation modifications from sialic acids. Mutations in this gene are associated with susceptibility to autoimmune disease 6. Multiple transcript variants encoding different isoforms, found either in the cytosol or in the lysosome, have been found for this gene.[provided by RefSeq, Feb 2011]

SIAE links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35417005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPA17	NM_017425.4 link	c.212A>G	p.Asn71Ser	missense_variant	Exon 3 of 5	ENST00000227135.7	NP_059121.1	Q15506A0A172Q397
SPA17	XM_011542870.3 link	c.212A>G	p.Asn71Ser	missense_variant	Exon 3 of 5		XP_011541172.1	Q15506A0A172Q397
SPA17	XM_024448583.2 link	c.212A>G	p.Asn71Ser	missense_variant	Exon 3 of 5		XP_024304351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPA17	ENST00000227135.7 link	c.212A>G	p.Asn71Ser	missense_variant	Exon 3 of 5	1	NM_017425.4	ENSP00000227135.2	Q15506
SPA17	ENST00000532692.1 link	c.212A>G	p.Asn71Ser	missense_variant	Exon 2 of 4	1		ENSP00000432305.1	Q15506
SPA17	ENST00000524614.1 link	n.163A>G		non_coding_transcript_exon_variant	Exon 2 of 5	3
SIAE	ENST00000525730.1 link	n.339-6044T>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000349

AC:

AN:

1431028

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712140

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.212A>G (p.N71S) alteration is located in exon 3 (coding exon 2) of the SPA17 gene. This alteration results from a A to G substitution at nucleotide position 212, causing the asparagine (N) at amino acid position 71 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.44

Sift

Benign

0.10

T;T

Sift4G

Benign

0.26

T;T

Polyphen

1.0

D;D

Vest4

0.26

MutPred

0.49

Gain of phosphorylation at N71 (P = 0.0595);Gain of phosphorylation at N71 (P = 0.0595);

MVP

0.14

MPC

0.090

ClinPred

0.98

GERP RS

5.8

Varity_R

0.15

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over