rs779765255
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003114.5(SPAG1):āc.890A>Gā(p.Glu297Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
SPAG1
NM_003114.5 missense
NM_003114.5 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 5.44
Genes affected
SPAG1 (HGNC:11212): (sperm associated antigen 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 agglutinating antibodies from an infertile woman. Furthermore, immunization of female rats with the recombinant human protein reduced fertility. This protein localizes to the plasma membrane of germ cells in the testis and to the post-acrosomal plasma membrane of mature spermatozoa. Recombinant polypeptide binds GTP and exhibits GTPase activity. Thus, this protein may regulate GTP signal transduction pathways involved in spermatogenesis and fertilization. Two transcript variants of this gene encode the same protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPAG1 | NM_003114.5 | c.890A>G | p.Glu297Gly | missense_variant | 9/19 | ENST00000388798.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPAG1 | ENST00000388798.7 | c.890A>G | p.Glu297Gly | missense_variant | 9/19 | 1 | NM_003114.5 | P1 | |
SPAG1 | ENST00000251809.4 | c.890A>G | p.Glu297Gly | missense_variant | 9/19 | 5 | P1 | ||
SPAG1 | ENST00000520508.5 | c.890A>G | p.Glu297Gly | missense_variant | 9/10 | 5 | |||
SPAG1 | ENST00000520643.5 | c.890A>G | p.Glu297Gly | missense_variant | 9/10 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251238Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135800
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461716Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727168
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GnomAD4 genome ? Cov.: 31
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31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces glutamic acid with glycine at codon 297 of the SPAG1 protein (p.Glu297Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs779765255, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Benign
T;D;T;D
Sift4G
Benign
T;D;T;D
Polyphen
1.0
.;D;.;D
Vest4
MutPred
Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);
MVP
MPC
0.64
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at