Variant chr8-100213070-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_003114.5(SPAG1):c.1097-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,439,426 control chromosomes in the GnomAD database, including 90,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8799 hom., cov: 33)

Exomes 𝑓: 0.35 ( 82032 hom. )

Consequence

SPAG1
NM_003114.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.630

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 links:

SPAG1 (HGNC:):

SPAG1 links:

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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 8-100213070-C-T is Benign according to our data. Variant chr8-100213070-C-T is described in ClinVar as [Benign]. Clinvar id is 262800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG1	NM_003114.5 linkuse as main transcript	c.1097-20C>T		intron_variant		ENST00000388798.7	NP_003105.2	Q07617-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SPAG1	ENST00000388798.7 linkuse as main transcript	c.1097-20C>T	intron_variant	1	NM_003114.5	ENSP00000373450.3	Q07617-1
SPAG1	ENST00000251809.4 linkuse as main transcript	c.1097-20C>T	intron_variant	5		ENSP00000251809.3	Q07617-1
SPAG1	ENST00000523302.1 linkuse as main transcript	n.-17C>T	upstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

49989

AN:

151520

Hom.:

8792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.362

AC:

21352

AN:

59054

Hom.:

4165

AF XY:

0.351

AC XY:

12374

AN XY:

35236

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.432

Gnomad SAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.354

AC:

455477

AN:

1287800

Hom.:

82032

Cov.:

AF XY:

0.352

AC XY:

223715

AN XY:

635522

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.295

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.330

AC:

50011

AN:

151626

Hom.:

8799

Cov.:

AF XY:

0.332

AC XY:

24571

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.450

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.325

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.312

Hom.:

944

Bravo

AF:

0.336

Asia WGS

AF:

0.385

AC:

1332

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over