rs74597335
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1
The ENST00000388798.7(SPAG1):c.474C>T(p.Tyr158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,499,358 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
SPAG1
ENST00000388798.7 synonymous
ENST00000388798.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.06
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 -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 8-100183422-C-T is Benign according to our data. Variant chr8-100183422-C-T is described in ClinVar as [Benign]. Clinvar id is 416526.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.06 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000191 (29/152174) while in subpopulation EAS AF= 0.0025 (13/5194). AF 95% confidence interval is 0.00148. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SPAG1 | NM_003114.5 | c.474C>T | p.Tyr158= | synonymous_variant | 5/19 | ENST00000388798.7 | NP_003105.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SPAG1 | ENST00000388798.7 | c.474C>T | p.Tyr158= | synonymous_variant | 5/19 | 1 | NM_003114.5 | ENSP00000373450 | P1 | |
| SPAG1 | ENST00000251809.4 | c.474C>T | p.Tyr158= | synonymous_variant | 5/19 | 5 | ENSP00000251809 | P1 | ||
| SPAG1 | ENST00000520508.5 | c.474C>T | p.Tyr158= | synonymous_variant | 5/10 | 5 | ENSP00000428070 | |||
| SPAG1 | ENST00000520643.5 | c.474C>T | p.Tyr158= | synonymous_variant | 5/10 | 2 | ENSP00000427716 |
Frequencies
GnomAD3 genomes 0.000191 AC: 29AN: 152056Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000223 AC: 53AN: 238098Hom.: 0 AF XY: 0.000240 AC XY: 31AN XY: 129240
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GnomAD4 exome AF: 0.000189 AC: 255AN: 1347184Hom.: 1 Cov.: 21 AF XY: 0.000198 AC XY: 134AN XY: 675194
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GnomAD4 genome 0.000191 AC: 29AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74400
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 28 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 21, 2023 | - - |
SPAG1-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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