rs35592493

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003114.5(SPAG1):c.669A>G(p.Gly223Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,588,374 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 300 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 568 hom. )

Consequence

SPAG1
NM_003114.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.15

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-100184701-A-G is Benign according to our data. Variant chr8-100184701-A-G is described in ClinVar as Benign. ClinVar VariationId is 416524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG1	NM_003114.5 link	c.669A>G	p.Gly223Gly	synonymous_variant	Exon 7 of 19	ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SPAG1	ENST00000388798.7 link	c.669A>G	p.Gly223Gly	synonymous_variant	Exon 7 of 19	1	NM_003114.5	ENSP00000373450.3
SPAG1	ENST00000251809.4 link	c.669A>G	p.Gly223Gly	synonymous_variant	Exon 7 of 19	5		ENSP00000251809.3
SPAG1	ENST00000520508.5 link	c.669A>G	p.Gly223Gly	synonymous_variant	Exon 7 of 10	5		ENSP00000428070.1
SPAG1	ENST00000520643.5 link	c.669A>G	p.Gly223Gly	synonymous_variant	Exon 7 of 10	2		ENSP00000427716.1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5617

AN:

152136

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.0470

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.0277

GnomAD2 exomes

AF:

0.0206

AC:

4629

AN:

224248

AF XY:

0.0193

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00587

Gnomad EAS exome

AF:

0.0996

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00926

AC:

13292

AN:

1436120

Hom.:

568

Cov.:

AF XY:

0.00977

AC XY:

6975

AN XY:

714264

show subpopulations

African (AFR)

AF:

0.111

AC:

3503

AN:

31586

American (AMR)

AF:

0.0139

AC:

528

AN:

37966

Ashkenazi Jewish (ASJ)

AF:

0.00481

AC:

123

AN:

25580

East Asian (EAS)

AF:

0.112

AC:

4270

AN:

37968

South Asian (SAS)

AF:

0.0391

AC:

3163

AN:

80922

European-Finnish (FIN)

AF:

0.0000564

AC:

AN:

53236

Middle Eastern (MID)

AF:

0.00944

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000631

AC:

697

AN:

1103802

Other (OTH)

AF:

0.0160

AC:

951

AN:

59340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

561

1121

1682

2242

2803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.0370

AC:

5639

AN:

152254

Hom.:

300

Cov.:

AF XY:

0.0373

AC XY:

2781

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.108

AC:

4490

AN:

41508

American (AMR)

AF:

0.0166

AC:

254

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3468

East Asian (EAS)

AF:

0.0999

AC:

518

AN:

5186

South Asian (SAS)

AF:

0.0468

AC:

226

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68024

Other (OTH)

AF:

0.0289

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

261

523

784

1046

1307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0153

Hom.:

Bravo

AF:

0.0412

Asia WGS

AF:

0.0750

AC:

260

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 04, 2019

GeneDx

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

- -

Primary ciliary dyskinesia

Benign:1

Jul 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.8

(source)

DANN

Benign

0.68

PhyloP100

-2.2

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

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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