rs1047991

Positions:

chr10-30340297-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018109.4(MTPAP):c.484C>T(p.Arg162Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,486 control chromosomes in the GnomAD database, including 58,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4671 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54324 hom. )

Consequence

MTPAP
NM_018109.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.89

Variant links:

Genes affected

MTPAP (HGNC:25532): (mitochondrial poly(A) polymerase) The protein encoded by this gene is a member of the DNA polymerase type-B-like family. This enzyme synthesizes the 3' poly(A) tail of mitochondrial transcripts and plays a role in replication-dependent histone mRNA degradation.[provided by RefSeq, Jan 2011]

MTPAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037120283).

BP6

Variant 10-30340297-G-A is Benign according to our data. Variant chr10-30340297-G-A is described in ClinVar as [Benign]. Clinvar id is 129624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-30340297-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTPAP	NM_018109.4 linkuse as main transcript	c.484C>T	p.Arg162Cys	missense_variant	3/9	ENST00000263063.9	NP_060579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTPAP	ENST00000263063.9 linkuse as main transcript	c.484C>T	p.Arg162Cys	missense_variant	3/9	1	NM_018109.4	ENSP00000263063	P1	Q9NVV4-1
MTPAP	ENST00000417581.1 linkuse as main transcript	c.289C>T	p.Arg97Cys	missense_variant	3/5	5		ENSP00000404392
MTPAP	ENST00000421701.1 linkuse as main transcript	c.370C>T	p.Arg124Cys	missense_variant	3/3	2		ENSP00000394118
MTPAP	ENST00000488290.5 linkuse as main transcript	n.2239C>T		non_coding_transcript_exon_variant	11/17	2

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37471

AN:

151920

Hom.:

4672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.246

AC:

61871

AN:

251446

Hom.:

8129

AF XY:

0.253

AC XY:

34380

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.227

Gnomad SAS exome

AF:

0.271

Gnomad FIN exome

AF:

0.217

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.270

AC:

394303

AN:

1461448

Hom.:

54324

Cov.:

AF XY:

0.270

AC XY:

196564

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.244

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.246

AC:

37467

AN:

152038

Hom.:

4671

Cov.:

AF XY:

0.243

AC XY:

18018

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.228

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.274

Hom.:

14977

Bravo

AF:

0.241

TwinsUK

AF:

0.275

AC:

1019

ALSPAC

AF:

0.278

AC:

1072

ESP6500AA

AF:

0.212

AC:

935

ESP6500EA

AF:

0.288

AC:

2476

ExAC

AF:

0.250

AC:

30348

Asia WGS

AF:

0.252

AC:

876

AN:

3478

EpiCase

AF:

0.288

EpiControl

AF:

0.288

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Spastic ataxia 4

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 20, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0070

DANN

Benign

0.60

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.38

T;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.26

N;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.069

T;T;T

Sift4G

Benign

0.067

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.032

MPC

0.49

ClinPred

0.015

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over