rs540994

chr10-30311297-A-C

Variant summary

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

The NM_018109.4(MTPAP):c.*2312T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,052 control chromosomes in the GnomAD database, including 17,011 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 0.45 (17011 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MTPAP NM_018109.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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]

(HGNC:):

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 = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTPAP	NM_018109.4	c.*2312T>G		3_prime_UTR_variant	9/9	ENST00000263063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTPAP	ENST00000263063.9	c.*2312T>G		3_prime_UTR_variant	9/9	1	NM_018109.4	P1
	ENST00000650129.1	n.853+463A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68932 AN: 151932 Hom.: 17010 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.490

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.453 AC: 68944 AN: 152052 Hom.: 17011 Cov.: 32 AF XY: 0.450 AC XY: 33428 AN XY: 74302

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.485

Alfa AF: 0.510 Hom.: 2615

Bravo AF: 0.450

Asia WGS AF: 0.301 AC: 1049 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	0.67
Dann	Benign	0.64

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: rs540994; hg19: chr10-30600226;