rs1047988

Positions:

• chr10-30340207-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.653

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 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
MTPAP	NM_018109.4	c.555+19C>T		intron_variant		ENST00000263063.9	NP_060579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTPAP	ENST00000263063.9	c.555+19C>T		intron_variant		1	NM_018109.4	ENSP00000263063.3
MTPAP	ENST00000421701.1	c.*7C>T		3_prime_UTR_variant	3/3	2		ENSP00000394118.1
MTPAP	ENST00000417581.1	c.360+19C>T		intron_variant		5		ENSP00000404392.1
MTPAP	ENST00000488290.5	n.2310+19C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38362 AN: 151916 Hom.: 4872 Cov.: 33

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

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.: 28 AF XY: 0.269 AC XY: 190540 AN XY: 707564

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.: 33 AF XY: 0.248 AC XY: 18455 AN XY: 74298

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

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

Other links and lift over

dbSNP: rs1047988; hg19: chr10-30629136;