chr8-100220285-G-A

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.76
Variant links:
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
SPAG1NM_003114.5 linkuse as main transcriptc.1542G>A p.Leu514= synonymous_variant 13/19 ENST00000388798.7
LOC105375669XR_928450.3 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPAG1ENST00000388798.7 linkuse as main transcriptc.1542G>A p.Leu514= synonymous_variant 13/191 NM_003114.5 P1Q07617-1
SPAG1ENST00000251809.4 linkuse as main transcriptc.1542G>A p.Leu514= synonymous_variant 13/195 P1Q07617-1
SPAG1ENST00000523302.1 linkuse as main transcriptn.343-4888G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00310
AC:
471
AN:
152172
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000724
Gnomad AMI
AF:
0.0340
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00763
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00447
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00284
AC:
692
AN:
243494
Hom.:
3
AF XY:
0.00273
AC XY:
359
AN XY:
131488
show subpopulations
Gnomad AFR exome
AF:
0.000558
Gnomad AMR exome
AF:
0.000527
Gnomad ASJ exome
AF:
0.00135
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00105
Gnomad FIN exome
AF:
0.00725
Gnomad NFE exome
AF:
0.00414
Gnomad OTH exome
AF:
0.00101
GnomAD4 exome
AF:
0.00365
AC:
5304
AN:
1454834
Hom.:
14
Cov.:
31
AF XY:
0.00355
AC XY:
2568
AN XY:
723540
show subpopulations
Gnomad4 AFR exome
AF:
0.000455
Gnomad4 AMR exome
AF:
0.000565
Gnomad4 ASJ exome
AF:
0.00116
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00129
Gnomad4 FIN exome
AF:
0.00725
Gnomad4 NFE exome
AF:
0.00407
Gnomad4 OTH exome
AF:
0.00367
GnomAD4 genome
AF:
0.00309
AC:
471
AN:
152290
Hom.:
2
Cov.:
33
AF XY:
0.00313
AC XY:
233
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000722
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00763
Gnomad4 NFE
AF:
0.00447
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00361
Hom.:
1
Bravo
AF:
0.00260
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00507
EpiControl
AF:
0.00397

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 submitterclinical testingInvitaeJan 29, 2024- -
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 30, 2016This 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 submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023SPAG1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
8.5
DANN
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117747863; hg19: chr8-101232513; COSMIC: COSV52561695; API