dbSNP rs145142638: SPATA17:p.Arg254Cys (chr1-217782210-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_138796.4(SPATA17):c.760C>T(p.Arg254Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000472 in 1,609,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

SPATA17
NM_138796.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

Publications

11 publications found

Variant links:

Genes affected

SPATA17 (HGNC:25184): (spermatogenesis associated 17) Predicted to enable calmodulin binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPATA17 links:

SPATA17-AS1 (HGNC:41086): (SPATA17 antisense RNA 1)

SPATA17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.833

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138796.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA17	NM_138796.4	MANE Select	c.760C>T	p.Arg254Cys	missense	Exon 8 of 11	NP_620151.1	Q96L03
SPATA17	NM_001375655.1		c.760C>T	p.Arg254Cys	missense	Exon 8 of 11	NP_001362584.1	Q96L03
SPATA17-AS1	NR_125784.1		n.249G>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA17	ENST00000366933.5	TSL:1 MANE Select	c.760C>T	p.Arg254Cys	missense	Exon 8 of 11	ENSP00000355900.4	Q96L03
SPATA17	ENST00000905764.1		c.760C>T	p.Arg254Cys	missense	Exon 8 of 12	ENSP00000575823.1
SPATA17	ENST00000937952.1		c.709C>T	p.Arg237Cys	missense	Exon 7 of 10	ENSP00000608011.1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000924

AC:

AN:

248830

AF XY:

0.0000891

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1457590

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

725202

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33276

American (AMR)

AF:

0.0000455

AC:

AN:

43910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39538

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85646

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53304

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

1110030

Other (OTH)

AF:

0.0000166

AC:

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.0000921

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41398

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000108

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000110

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.7

PhyloP100

4.6

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MVP

0.68

MPC

0.21

ClinPred

0.95

GERP RS

4.7

Varity_R

0.58

gMVP

0.62

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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