10-30327945-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018109.4(MTPAP):c.781-1310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,034 control chromosomes in the GnomAD database, including 15,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (15348 hom., cov: 32)
• Consequence: MTPAP NM_018109.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTPAP	NM_018109.4	c.781-1310A>G		intron_variant		ENST00000263063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTPAP	ENST00000263063.9	c.781-1310A>G		intron_variant		1	NM_018109.4	P1
MTPAP	ENST00000417581.1	c.586-1310A>G		intron_variant		5
MTPAP	ENST00000488290.5	n.2536-1310A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61356 AN: 151920 Hom.: 15345 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.404 AC: 61355 AN: 152034 Hom.: 15348 Cov.: 32 AF XY: 0.402 AC XY: 29897 AN XY: 74286

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.443

Alfa AF: 0.474 Hom.: 2350

Bravo AF: 0.395

Asia WGS AF: 0.276 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.3
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs959629; hg19: chr10-30616874;