Variant rs34959427 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018109.4(MTPAP):c.781-54A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,379,008 control chromosomes in the GnomAD database, including 1,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 103 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1136 hom. )

Consequence

MTPAP
NM_018109.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.63

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=-0.78).

BP6

Variant 10-30326689-T-A is Benign according to our data. Variant chr10-30326689-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0313 (4765/152298) while in subpopulation NFE AF= 0.045 (3059/68032). AF 95% confidence interval is 0.0436. There are 103 homozygotes in gnomad4. There are 2239 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 103 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTPAP	NM_018109.4 linkuse as main transcript	c.781-54A>T		intron_variant		ENST00000263063.9	NP_060579.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MTPAP	ENST00000263063.9 linkuse as main transcript	c.781-54A>T	intron_variant	1	NM_018109.4	ENSP00000263063	P1	Q9NVV4-1
MTPAP	ENST00000417581.1 linkuse as main transcript	c.586-54A>T	intron_variant	5		ENSP00000404392
MTPAP	ENST00000488290.5 linkuse as main transcript	n.2536-54A>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4769

AN:

152180

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00869

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.0392

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0468

GnomAD4 exome

AF:

0.0398

AC:

48855

AN:

1226710

Hom.:

1136

AF XY:

0.0392

AC XY:

24381

AN XY:

621784

show subpopulations

Gnomad4 AFR exome

AF:

0.00804

Gnomad4 AMR exome

AF:

0.0268

Gnomad4 ASJ exome

AF:

0.0501

Gnomad4 EAS exome

AF:

0.0000519

Gnomad4 SAS exome

AF:

0.0194

Gnomad4 FIN exome

AF:

0.0409

Gnomad4 NFE exome

AF:

0.0448

Gnomad4 OTH exome

AF:

0.0381

GnomAD4 genome

AF:

0.0313

AC:

4765

AN:

152298

Hom.:

103

Cov.:

AF XY:

0.0301

AC XY:

2239

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00866

Gnomad4 AMR

AF:

0.0343

Gnomad4 ASJ

AF:

0.0528

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.0392

Gnomad4 NFE

AF:

0.0450

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0413

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.1

DANN

Benign

0.71

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