8-100213070-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SPAG1	NM_003114.5 link	c.1097-20C>T		intron_variant	Intron 10 of 18	ENST00000388798.7	NP_003105.2

Ensembl

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

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

GnomAD2 exomes

AF:

0.362

AC:

21352

AN:

59054

AF XY:

0.351

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 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

African (AFR)

AF:

0.213

AC:

5369

AN:

25172

American (AMR)

AF:

0.479

AC:

9328

AN:

19470

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

7405

AN:

21904

East Asian (EAS)

AF:

0.492

AC:

13515

AN:

27494

South Asian (SAS)

AF:

0.295

AC:

20671

AN:

69972

European-Finnish (FIN)

AF:

0.321

AC:

10105

AN:

31482

Middle Eastern (MID)

AF:

0.315

AC:

1609

AN:

5114

European-Non Finnish (NFE)

AF:

0.357

AC:

369065

AN:

1034498

Other (OTH)

AF:

0.349

AC:

18410

AN:

52694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

14314

28628

42942

57256

71570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12276

24552

36828

49104

61380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.330

AC:

50011

AN:

151626

Hom.:

8799

Cov.:

AF XY:

0.332

AC XY:

24571

AN XY:

74120

show subpopulations

African (AFR)

AF:

0.224

AC:

9217

AN:

41088

American (AMR)

AF:

0.450

AC:

6885

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1207

AN:

3470

East Asian (EAS)

AF:

0.508

AC:

2625

AN:

5164

South Asian (SAS)

AF:

0.300

AC:

1448

AN:

4822

European-Finnish (FIN)

AF:

0.325

AC:

3430

AN:

10554

Middle Eastern (MID)

AF:

0.332

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.355

AC:

24085

AN:

67930

Other (OTH)

AF:

0.331

AC:

699

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1713

3427

5140

6854

8567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Dec 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 28

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over