4-52072099-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_145263.4(SPATA18):c.701G>A(p.Arg234Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,614,012 control chromosomes in the GnomAD database, including 17 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 16 hom. )

Consequence

SPATA18
NM_145263.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.260

Publications

6 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005424261).

BP6

Variant 4-52072099-G-A is Benign according to our data. Variant chr4-52072099-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 714198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

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.701G>A	p.Arg234Gln	missense	Exon 6 of 13	NP_660306.1	Q8TC71-1
SPATA18	NM_001297608.2		c.605G>A	p.Arg202Gln	missense	Exon 5 of 12	NP_001284537.1	Q8TC71-2
SPATA18	NM_001346102.2		c.290G>A	p.Arg97Gln	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.701G>A	p.Arg234Gln	missense	Exon 6 of 13	ENSP00000295213.4	Q8TC71-1
SPATA18	ENST00000419395.6	TSL:2	c.605G>A	p.Arg202Gln	missense	Exon 5 of 12	ENSP00000415309.2	Q8TC71-2
SPATA18	ENST00000851879.1		c.701G>A	p.Arg234Gln	missense	Exon 6 of 12	ENSP00000521938.1

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

311

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000777

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00211

AC:

531

AN:

251226

AF XY:

0.00218

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00349

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00369

AC:

5395

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

2527

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33480

American (AMR)

AF:

0.00143

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

26136

East Asian (EAS)

AF:

0.00108

AC:

AN:

39700

South Asian (SAS)

AF:

0.000313

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000374

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00447

AC:

4974

AN:

1112000

Other (OTH)

AF:

0.00338

AC:

204

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

317

633

950

1266

1583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<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:

0.00204

AC:

311

AN:

152138

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

141

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000891

AC:

AN:

41518

American (AMR)

AF:

0.000851

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.000779

AC:

AN:

5136

South Asian (SAS)

AF:

0.000831

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00359

AC:

244

AN:

68012

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.00344

Hom.:

Bravo

AF:

0.00250

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00213

AC:

258

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00333

EpiControl

AF:

0.00367

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.1

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.045

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.67

M_CAP

Benign

0.022

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.7

PhyloP100

0.26

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.7

REVEL

Benign

0.053

Sift

Benign

0.19

Sift4G

Benign

0.16

Polyphen

0.028

Vest4

0.062

MVP

0.17

MPC

0.18

ClinPred

0.0028

GERP RS

0.30

Varity_R

0.037

gMVP

0.14

Mutation Taster

=100/0

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

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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