Genetic Variant SPAG1:c.1097-20C>G (chr8-100213070-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003114.5(SPAG1):c.1097-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPAG1
NM_003114.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.630

Publications

5 publications found

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]

SPAG1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 28
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPAG1 links:

ENSG00000302563 (HGNC:):

ENSG00000302563 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG1	NM_003114.5 link	c.1097-20C>G		intron_variant	Intron 10 of 18	ENST00000388798.7	NP_003105.2	Q07617-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPAG1	ENST00000388798.7 link	c.1097-20C>G	intron_variant	Intron 10 of 18	1	NM_003114.5	ENSP00000373450.3	Q07617-1
SPAG1	ENST00000251809.4 link	c.1097-20C>G	intron_variant	Intron 10 of 18	5		ENSP00000251809.3	Q07617-1
SPAG1	ENST00000523302.1 link	n.-17C>G	upstream_gene_variant		3
ENSG00000302563	ENST00000787874.1 link	n.-129G>C	upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1289648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

636448

African (AFR)

AF:

0.00

AC:

AN:

25200

American (AMR)

AF:

0.00

AC:

AN:

19566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21952

East Asian (EAS)

AF:

0.00

AC:

AN:

27546

South Asian (SAS)

AF:

0.00

AC:

AN:

70194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5130

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1035670

Other (OTH)

AF:

0.00

AC:

AN:

52816

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over