NM_017425.4:c.41A>G

Variant names:

• chr11-124675305-A-G
• rs753028777
• NM_017425.4:c.41A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017425.4(SPA17):​c.41A>G​(p.Gln14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,838 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. Q14L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SPA17 NM_017425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 1 publications found

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]

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 Gene-Disease associations (from GenCC):

• autoimmune disease, susceptibility to, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

LOC124902780 (HGNC:):

ACMG classification

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=0.1418283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017425.4. 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
	SPA17	NM_017425.4	MANE Select	c.41A>G	p.Gln14Arg	missense	Exon 2 of 5	NP_059121.1	A0A172Q397
	SIAE	NM_001199922.2		c.-86T>C		5_prime_UTR	Exon 3 of 12	NP_001186851.1	Q9HAT2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPA17	ENST00000227135.7	TSL:1 MANE Select	c.41A>G	p.Gln14Arg	missense	Exon 2 of 5	ENSP00000227135.2	Q15506
	SPA17	ENST00000532692.1	TSL:1	c.41A>G	p.Gln14Arg	missense	Exon 1 of 4	ENSP00000432305.1	Q15506
	SIAE	ENST00000618733.4	TSL:1	c.-86T>C		5_prime_UTR	Exon 3 of 12	ENSP00000478211.1	Q9HAT2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461838 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.78
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.76	N
PhyloP100		3.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.098
Sift	Benign	0.65	T
Sift4G	Benign	0.88	T
Polyphen		0.10	B
Vest4		0.25
MutPred		0.40		Gain of methylation at Q14 (P = 0.0314)
MVP		0.68
MPC		0.021
ClinPred		0.36	T
GERP RS		4.4
PromoterAI		-0.0074	Neutral
Varity_R		0.090
gMVP		0.61
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs753028777; hg19: chr11-124545201;