rs35252724
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003114.5(SPAG1):c.1584G>A(p.Ala528Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000575 in 1,614,090 control chromosomes in the GnomAD database, including 7 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 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 4 hom. )
Consequence
SPAG1
NM_003114.5 synonymous
NM_003114.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.408
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 8-100220327-G-A is Benign according to our data. Variant chr8-100220327-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.408 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00312 (476/152328) while in subpopulation AFR AF= 0.011 (459/41572). AF 95% confidence interval is 0.0102. There are 3 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SPAG1 | ENST00000388798.7 | c.1584G>A | p.Ala528Ala | synonymous_variant | Exon 13 of 19 | 1 | NM_003114.5 | ENSP00000373450.3 | ||
| SPAG1 | ENST00000251809.4 | c.1584G>A | p.Ala528Ala | synonymous_variant | Exon 13 of 19 | 5 | ENSP00000251809.3 | |||
| SPAG1 | ENST00000523302.1 | n.343-4846G>A | intron_variant | Intron 1 of 2 | 3 |
Frequencies
GnomAD3 genomes 0.00311 AC: 474AN: 152210Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.000760 AC: 191AN: 251304Hom.: 3 AF XY: 0.000589 AC XY: 80AN XY: 135812
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GnomAD4 exome AF: 0.000309 AC: 452AN: 1461762Hom.: 4 Cov.: 31 AF XY: 0.000261 AC XY: 190AN XY: 727188
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GnomAD4 genome 0.00312 AC: 476AN: 152328Hom.: 3 Cov.: 33 AF XY: 0.00282 AC XY: 210AN XY: 74490
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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:2
Jan 24, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
May 03, 2022
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Primary ciliary dyskinesia Benign:1
Oct 19, 2016
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This alteration is classified as 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. -
Computational scores
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Name
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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