Genetic Variant SPATA18:p.Glu181Lys (chr4-52071939-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_145263.4(SPATA18):c.541G>A(p.Glu181Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SPATA18
NM_145263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

Publications

0 publications found

Variant links:

Genes affected

SPATA18 (HGNC:29579): (spermatogenesis associated 18) This gene encodes a p53-inducible protein that is able to induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins, thereby contributing to mitochondrial quality control. Dysregulation of mitochondrial quality control is associated with cancer and degenerative diseases. The encoded protein mediates accumulation of the lysosome-like mitochondrial organelles through interaction with B cell lymphoma 2 interacting protein 3 and B cell lymphoma 2 interacting protein 3 like at the outer mitochondrial membrane, which allows translocation of lysosomal proteins to the mitochondrial matrix from the cytosol. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

SPATA18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33964962).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA18	NM_145263.4	MANE Select	c.541G>A	p.Glu181Lys	missense	Exon 6 of 13	NP_660306.1	Q8TC71-1
SPATA18	NM_001297608.2		c.445G>A	p.Glu149Lys	missense	Exon 5 of 12	NP_001284537.1	Q8TC71-2
SPATA18	NM_001346102.2		c.130G>A	p.Glu44Lys	missense	Exon 4 of 11	NP_001333031.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA18	ENST00000295213.9	TSL:1 MANE Select	c.541G>A	p.Glu181Lys	missense	Exon 6 of 13	ENSP00000295213.4	Q8TC71-1
SPATA18	ENST00000419395.6	TSL:2	c.445G>A	p.Glu149Lys	missense	Exon 5 of 12	ENSP00000415309.2	Q8TC71-2
SPATA18	ENST00000851879.1		c.541G>A	p.Glu181Lys	missense	Exon 6 of 12	ENSP00000521938.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.0000160

AC:

AN:

250734

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000895

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1111994

Other (OTH)

AF:

0.0000166

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

0.00000659

AC:

AN:

151800

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41294

American (AMR)

AF:

0.0000657

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

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

0.28

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

0.11

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.040

MetaRNN

Benign

0.34

MetaSVM

Uncertain

0.79

MutationAssessor

Uncertain

2.4

PhyloP100

4.4

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.41

Sift

Uncertain

0.021

Sift4G

Benign

0.29

Polyphen

1.0

Vest4

0.46

MutPred

0.17

Gain of MoRF binding (P = 0.0175)

MVP

0.45

MPC

0.68

ClinPred

0.91

GERP RS

4.9

Varity_R

0.20

gMVP

0.23

Mutation Taster

=87/13

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