8-100194231-A-AGAC

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_003114.5(SPAG1):c.1059_1060insGAC(p.Lys353_Ser354insAsp) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,603,786 control chromosomes in the GnomAD database, including 32,931 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2435 hom., cov: 29)

Exomes 𝑓: 0.20 ( 30496 hom. )

Consequence

SPAG1
NM_003114.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.19

Publications

10 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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_003114.5

BP6

Variant 8-100194231-A-AGAC is Benign according to our data. Variant chr8-100194231-A-AGAC is described in ClinVar as Benign. ClinVar VariationId is 221008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 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	HGVSp	Effect	Exon Rank	Protein	UniProt
SPAG1	NM_003114.5	MANE Select	c.1059_1060insGAC	p.Lys353_Ser354insAsp	conservative_inframe_insertion	Exon 10 of 19	NP_003105.2
SPAG1	NM_001374321.1		c.1059_1060insGAC	p.Lys353_Ser354insAsp	conservative_inframe_insertion	Exon 10 of 19	NP_001361250.1	Q07617-1
SPAG1	NM_172218.3		c.1059_1060insGAC	p.Lys353_Ser354insAsp	conservative_inframe_insertion	Exon 10 of 19	NP_757367.1	Q07617-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPAG1	ENST00000388798.7	TSL:1 MANE Select	c.1059_1060insGAC	p.Lys353_Ser354insAsp	conservative_inframe_insertion	Exon 10 of 19	ENSP00000373450.3	Q07617-1
SPAG1	ENST00000251809.4	TSL:5	c.1059_1060insGAC	p.Lys353_Ser354insAsp	conservative_inframe_insertion	Exon 10 of 19	ENSP00000251809.3	Q07617-1
SPAG1	ENST00000964470.1		c.1059_1060insGAC	p.Lys353_Ser354insAsp	conservative_inframe_insertion	Exon 10 of 19	ENSP00000634529.1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25464

AN:

152052

Hom.:

2438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.0717

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.194

AC:

48036

AN:

248246

AF XY:

0.199

show subpopulations

Gnomad AFR exome

AF:

0.0700

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.0536

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.200

AC:

289875

AN:

1451616

Hom.:

30496

Cov.:

AF XY:

0.201

AC XY:

145532

AN XY:

722402

show subpopulations

African (AFR)

AF:

0.0646

AC:

2152

AN:

33328

American (AMR)

AF:

0.206

AC:

9138

AN:

44364

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5833

AN:

26000

East Asian (EAS)

AF:

0.0784

AC:

3101

AN:

39548

South Asian (SAS)

AF:

0.244

AC:

20812

AN:

85436

European-Finnish (FIN)

AF:

0.255

AC:

13577

AN:

53268

Middle Eastern (MID)

AF:

0.241

AC:

1384

AN:

5740

European-Non Finnish (NFE)

AF:

0.201

AC:

222063

AN:

1103928

Other (OTH)

AF:

0.197

AC:

11815

AN:

60004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

10757

21515

32272

43030

53787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7596

15192

22788

30384

37980

<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:

0.167

AC:

25459

AN:

152170

Hom.:

2435

Cov.:

AF XY:

0.169

AC XY:

12545

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0746

AC:

3099

AN:

41550

American (AMR)

AF:

0.180

AC:

2747

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

791

AN:

3472

East Asian (EAS)

AF:

0.0717

AC:

372

AN:

5190

South Asian (SAS)

AF:

0.227

AC:

1096

AN:

4820

European-Finnish (FIN)

AF:

0.245

AC:

2589

AN:

10548

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14179

AN:

67982

Other (OTH)

AF:

0.184

AC:

390

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1058

2115

3173

4230

5288

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:

0.203

Hom.:

579

Bravo

AF:

0.157

Asia WGS

AF:

0.149

AC:

520

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Primary ciliary dyskinesia (1)

Primary ciliary dyskinesia 28 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=68/32

polymorphism

(source)

Splicing

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