dbSNP rs139217290: MTPAP:c.158-9C>T (chr10-30341649-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018109.4(MTPAP):c.158-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,613,574 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 6 hom. )

Consequence

MTPAP
NM_018109.4 intron

Scores

Splicing: ADA: 0.00002277

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.34

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 10-30341649-G-A is Benign according to our data. Variant chr10-30341649-G-A is described in ClinVar as [Benign]. Clinvar id is 378178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-30341649-G-A is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTPAP	NM_018109.4 link	c.158-9C>T		intron_variant	Intron 1 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.158-9C>T	intron_variant	Intron 1 of 8	1	NM_018109.4	ENSP00000263063.3	Q9NVV4-1
MTPAP	ENST00000417581.1 link	c.-38-9C>T	intron_variant	Intron 1 of 4	5		ENSP00000404392.1	Q5T852
MTPAP	ENST00000421701.1 link	c.44-9C>T	intron_variant	Intron 1 of 2	2		ENSP00000394118.1	Q5T851
MTPAP	ENST00000488290.5 link	n.1913-9C>T	intron_variant	Intron 9 of 16	2

Frequencies

GnomAD3 genomes

AF:

0.00462

AC:

703

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00141

AC:

355

AN:

250892

Hom.:

AF XY:

0.00118

AC XY:

160

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00250

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000528

AC:

772

AN:

1461332

Hom.:

Cov.:

AF XY:

0.000506

AC XY:

368

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00156

Gnomad4 SAS exome

AF:

0.000881

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.00462

AC:

704

AN:

152242

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

341

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00534

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 09, 2015

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. -

Feb 10, 2021

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Sep 18, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.082

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