10-30313463-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018109.4(MTPAP):c.*146G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,126,550 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (20 hom., cov: 32)
  • Exomes 𝑓: 0.014 (132 hom.)
• Consequence: MTPAP NM_018109.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.776

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-30313463-C-T is Benign according to our data. Variant chr10-30313463-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1551/152248) while in subpopulation NFE AF= 0.0159 (1080/68012). AF 95% confidence interval is 0.0151. There are 20 homozygotes in gnomad4. There are 732 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTPAP	NM_018109.4	c.*146G>A		3_prime_UTR_variant	9/9	ENST00000263063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTPAP	ENST00000263063.9	c.*146G>A		3_prime_UTR_variant	9/9	1	NM_018109.4	P1
MTPAP	ENST00000488290.5	n.3650G>A		non_coding_transcript_exon_variant	17/17	2

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1551 AN: 152130 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00962

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00547

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.0137 AC: 13303 AN: 974302 Hom.: 132 Cov.: 13 AF XY: 0.0139 AC XY: 6969 AN XY: 502204

Gnomad4 AFR exome AF: 0.00220

Gnomad4 AMR exome AF: 0.00877

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.0000268

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.00720

Gnomad4 NFE exome AF: 0.0150

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0102 AC: 1551 AN: 152248 Hom.: 20 Cov.: 32 AF XY: 0.00983 AC XY: 732 AN XY: 74442

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.00961

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00547

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0136 Hom.: 3

Bravo AF: 0.0103

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.4
Dann	Benign	0.55

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: rs34660258; hg19: chr10-30602392;