rs971341609

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003114.5(SPAG1):c.1229C>G(p.Pro410Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,393,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P410P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

SPAG1
NM_003114.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.125

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.101653814).

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.1229C>G	p.Pro410Arg	missense	Exon 11 of 19	NP_003105.2
SPAG1	NM_001374321.1		c.1229C>G	p.Pro410Arg	missense	Exon 11 of 19	NP_001361250.1	Q07617-1
SPAG1	NM_172218.3		c.1229C>G	p.Pro410Arg	missense	Exon 11 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.1229C>G	p.Pro410Arg	missense	Exon 11 of 19	ENSP00000373450.3	Q07617-1
SPAG1	ENST00000251809.4	TSL:5	c.1229C>G	p.Pro410Arg	missense	Exon 11 of 19	ENSP00000251809.3	Q07617-1
SPAG1	ENST00000964470.1		c.1229C>G	p.Pro410Arg	missense	Exon 11 of 19	ENSP00000634529.1

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000425

AC:

AN:

47022

AF XY:

0.0000699

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000306

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000322

AC:

AN:

1242678

Hom.:

Cov.:

AF XY:

0.00000327

AC XY:

AN XY:

612122

show subpopulations

African (AFR)

AF:

0.0000822

AC:

AN:

24322

American (AMR)

AF:

0.000119

AC:

AN:

16874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19920

East Asian (EAS)

AF:

0.00

AC:

AN:

26202

South Asian (SAS)

AF:

0.00

AC:

AN:

64070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1007592

Other (OTH)

AF:

0.00

AC:

AN:

49928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000399

AC:

AN:

150332

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73402

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41220

American (AMR)

AF:

0.0000663

AC:

AN:

15080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67486

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000604

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia 28 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.022

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.32

M_CAP

Benign

0.073

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.13

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.5

REVEL

Benign

0.074

Sift

Benign

0.057

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.11

MVP

0.55

MPC

0.16

ClinPred

0.060

GERP RS

-0.45

Varity_R

0.045

gMVP

0.28

Mutation Taster

=92/8

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over