rs150489876

chr10-30340295-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_018109.4(MTPAP):c.486C>T(p.Arg162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,614,116 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: MTPAP NM_018109.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.264

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-30340295-G-A is Benign according to our data. Variant chr10-30340295-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 586159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.264 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTPAP	NM_018109.4	c.486C>T	p.Arg162=	synonymous_variant	3/9	ENST00000263063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTPAP	ENST00000263063.9	c.486C>T	p.Arg162=	synonymous_variant	3/9	1	NM_018109.4	P1
MTPAP	ENST00000417581.1	c.291C>T	p.Arg97=	synonymous_variant	3/5	5
MTPAP	ENST00000421701.1	c.372C>T	p.Arg124=	synonymous_variant	3/3	2
MTPAP	ENST00000488290.5	n.2241C>T		non_coding_transcript_exon_variant	11/17	2

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000346 AC: 87 AN: 251462 Hom.: 0 AF XY: 0.000471 AC XY: 64 AN XY: 135898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00235

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000178 AC: 260 AN: 1461850 Hom.: 2 Cov.: 32 AF XY: 0.000264 AC XY: 192 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00253

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74440

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000416

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 24, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.5
Dann	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150489876; hg19: chr10-30629224; COSMIC: COSV99554460;