rs117747863
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_003114.5(SPAG1):c.1542G>A(p.Leu514=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,607,124 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0036 ( 14 hom. )
Consequence
SPAG1
NM_003114.5 synonymous
NM_003114.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 7.76
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 Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 8-100220285-G-A is Benign according to our data. Variant chr8-100220285-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00309 (471/152290) while in subpopulation NFE AF= 0.00447 (304/68022). AF 95% confidence interval is 0.00406. There are 2 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| SPAG1 | NM_003114.5 | c.1542G>A | p.Leu514= | synonymous_variant | 13/19 | ENST00000388798.7 | |
| LOC105375669 | XR_928450.3 | upstream_gene_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SPAG1 | ENST00000388798.7 | c.1542G>A | p.Leu514= | synonymous_variant | 13/19 | 1 | NM_003114.5 | P1 | |
| SPAG1 | ENST00000251809.4 | c.1542G>A | p.Leu514= | synonymous_variant | 13/19 | 5 | P1 | ||
| SPAG1 | ENST00000523302.1 | n.343-4888G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00310 AC: 471AN: 152172Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00284 AC: 692AN: 243494Hom.: 3 AF XY: 0.00273 AC XY: 359AN XY: 131488
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GnomAD4 exome AF: 0.00365 AC: 5304AN: 1454834Hom.: 14 Cov.: 31 AF XY: 0.00355 AC XY: 2568AN XY: 723540
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GnomAD4 genome ? AF: 0.00309 AC: 471AN: 152290Hom.: 2 Cov.: 33 AF XY: 0.00313 AC XY: 233AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 28 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Primary ciliary dyskinesia Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | SPAG1: BP4, BS2 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at