dbSNP rs1047988: MTPAP:c.555+19C>T (chr10-30340207-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_018109.4(MTPAP):c.555+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,569,076 control chromosomes in the GnomAD database, including 57,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4871 hom., cov: 33)

Exomes 𝑓: 0.27 ( 52292 hom. )

Consequence

MTPAP
NM_018109.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.653

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 (BayesDel_noAF=-0.9).

BP6

Variant 10-30340207-G-A is Benign according to our data. Variant chr10-30340207-G-A is described in ClinVar as [Benign]. Clinvar id is 138281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-30340207-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 rank	MANE	Protein	UniProt
MTPAP	NM_018109.4 link	c.555+19C>T		intron_variant	Intron 3 of 8	ENST00000263063.9	NP_060579.3	Q9NVV4-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MTPAP	ENST00000263063.9 link	c.555+19C>T	intron_variant	Intron 3 of 8	1	NM_018109.4	ENSP00000263063.3	Q9NVV4-1
MTPAP	ENST00000421701 link	c.*7C>T	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000394118.1	Q5T851
MTPAP	ENST00000417581.1 link	c.360+19C>T	intron_variant	Intron 3 of 4	5		ENSP00000404392.1	Q5T852
MTPAP	ENST00000488290.5 link	n.2310+19C>T	intron_variant	Intron 11 of 16	2

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38362

AN:

151916

Hom.:

4872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.247

AC:

61829

AN:

250128

Hom.:

8085

AF XY:

0.254

AC XY:

34335

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.325

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.269

AC:

380502

AN:

1417042

Hom.:

52292

Cov.:

AF XY:

0.269

AC XY:

190540

AN XY:

707564

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.252

AC:

38358

AN:

152034

Hom.:

4871

Cov.:

AF XY:

0.248

AC XY:

18455

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.270

Hom.:

1994

Bravo

AF:

0.248

Asia WGS

AF:

0.252

AC:

878

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 06, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spastic ataxia 4

Benign:3

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.6

DANN

Benign

0.62

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

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