rs1762598

Variant names:

• chr10-30352501-G-A
• rs1762598
• ENST00000488290.5:n.1913-10861C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000488290.5(MTPAP):​n.1913-10861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,070 control chromosomes in the GnomAD database, including 4,811 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 0.25 (4811 hom., cov: 32)
• Consequence: MTPAP ENST00000488290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• spastic ataxia 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488290.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTPAP	ENST00000488290.5	TSL:2	n.1913-10861C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38112 AN: 151952 Hom.: 4813 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.251 AC: 38119 AN: 152070 Hom.: 4811 Cov.: 32 AF XY: 0.246 AC XY: 18308 AN XY: 74312

African (AFR) AF: 0.245 AC: 10152 AN: 41484

American (AMR) AF: 0.192 AC: 2937 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3470

East Asian (EAS) AF: 0.180 AC: 929 AN: 5174

South Asian (SAS) AF: 0.268 AC: 1288 AN: 4806

European-Finnish (FIN) AF: 0.220 AC: 2326 AN: 10582

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18675 AN: 67964

Other (OTH) AF: 0.250 AC: 525 AN: 2104

Alfa AF: 0.268 Hom.: 23198

Bravo AF: 0.247

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1762598;

hg19: chr10-30641430;