Genetic Variant SPATA17:p.Glu281Lys (chr1-217782291-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138796.4(SPATA17):c.841G>A(p.Glu281Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,609,826 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SPATA17
NM_138796.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.873

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03549856).

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.841G>A	p.Glu281Lys	missense	Exon 8 of 11	NP_620151.1	Q96L03
SPATA17	NM_001375655.1		c.841G>A	p.Glu281Lys	missense	Exon 8 of 11	NP_001362584.1	Q96L03
SPATA17-AS1	NR_125784.1		n.168C>T		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.841G>A	p.Glu281Lys	missense	Exon 8 of 11	ENSP00000355900.4	Q96L03
SPATA17	ENST00000905764.1		c.841G>A	p.Glu281Lys	missense	Exon 8 of 12	ENSP00000575823.1
SPATA17	ENST00000937952.1		c.790G>A	p.Glu264Lys	missense	Exon 7 of 10	ENSP00000608011.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

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:

0.0000242

AC:

AN:

248348

AF XY:

0.0000372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1457654

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33234

American (AMR)

AF:

0.00

AC:

AN:

43904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25964

East Asian (EAS)

AF:

0.000228

AC:

AN:

39558

South Asian (SAS)

AF:

0.00

AC:

AN:

85700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110086

Other (OTH)

AF:

0.00

AC:

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

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:

0.0000131

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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.:

ExAC

AF:

0.0000330

AC:

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

0.059

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.9

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.031

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.70

M_CAP

Benign

0.014

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.87

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.1

REVEL

Benign

0.028

Sift

Benign

0.32

Sift4G

Benign

0.10

Polyphen

0.0020

Vest4

0.21

MutPred

0.36

Gain of helix (P = 0.0082)

MVP

0.32

MPC

0.025

ClinPred

0.024

GERP RS

-2.3

Varity_R

0.053

gMVP

0.34

Mutation Taster

=98/2

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