chr8-100191509-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003114.5(SPAG1):c.939+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,548,334 control chromosomes in the GnomAD database, including 32,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2456 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30022 hom. )

Consequence

SPAG1
NM_003114.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.127

Publications

8 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), G2P, PanelApp Australia, ClinGen
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-100191509-T-C is Benign according to our data. Variant chr8-100191509-T-C is described in ClinVar as Benign. ClinVar VariationId is 262804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003114.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPAG1	NM_003114.5	MANE Select	c.939+13T>C	intron	N/A	NP_003105.2
SPAG1	NM_001374321.1		c.939+13T>C	intron	N/A	NP_001361250.1	Q07617-1
SPAG1	NM_172218.3		c.939+13T>C	intron	N/A	NP_757367.1	Q07617-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPAG1	ENST00000388798.7	TSL:1 MANE Select	c.939+13T>C	intron	N/A	ENSP00000373450.3	Q07617-1
SPAG1	ENST00000251809.4	TSL:5	c.939+13T>C	intron	N/A	ENSP00000251809.3	Q07617-1
SPAG1	ENST00000964470.1		c.939+13T>C	intron	N/A	ENSP00000634529.1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25513

AN:

152082

Hom.:

2459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.0722

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.199

AC:

48737

AN:

245260

AF XY:

0.204

show subpopulations

Gnomad AFR exome

AF:

0.0716

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.0562

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.203

AC:

283893

AN:

1396134

Hom.:

30022

Cov.:

AF XY:

0.205

AC XY:

142912

AN XY:

698032

show subpopulations

African (AFR)

AF:

0.0666

AC:

2125

AN:

31910

American (AMR)

AF:

0.211

AC:

9189

AN:

43606

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

5812

AN:

25642

East Asian (EAS)

AF:

0.0795

AC:

3131

AN:

39360

South Asian (SAS)

AF:

0.247

AC:

20739

AN:

83824

European-Finnish (FIN)

AF:

0.256

AC:

13605

AN:

53210

Middle Eastern (MID)

AF:

0.243

AC:

1371

AN:

5638

European-Non Finnish (NFE)

AF:

0.205

AC:

216283

AN:

1054668

Other (OTH)

AF:

0.200

AC:

11638

AN:

58276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

10796

21592

32388

43184

53980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7284

14568

21852

29136

36420

<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:

0.168

AC:

25508

AN:

152200

Hom.:

2456

Cov.:

AF XY:

0.169

AC XY:

12589

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0747

AC:

3103

AN:

41552

American (AMR)

AF:

0.180

AC:

2753

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

791

AN:

3470

East Asian (EAS)

AF:

0.0722

AC:

374

AN:

5182

South Asian (SAS)

AF:

0.228

AC:

1102

AN:

4830

European-Finnish (FIN)

AF:

0.247

AC:

2610

AN:

10564

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14189

AN:

68006

Other (OTH)

AF:

0.185

AC:

389

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1107

2213

3320

4426

5533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.201

Hom.:

4408

Bravo

AF:

0.157

Asia WGS

AF:

0.150

AC:

522

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Primary ciliary dyskinesia 28 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.0

(source)

DANN

Benign

0.65

PhyloP100

0.13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over