10-30319128-A-G

Variant names:

• chr10-30319128-A-G
• rs639299
• NM_018109.4:c.1220-2918T>C

Variant summary

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

The NM_018109.4(MTPAP):​c.1220-2918T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,916 control chromosomes in the GnomAD database, including 25,906 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 0.56 (25906 hom., cov: 31)
• Consequence: MTPAP NM_018109.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 8 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018109.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTPAP	NM_018109.4	MANE Select	c.1220-2918T>C		intron	N/A	NP_060579.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTPAP	ENST00000263063.9	TSL:1 MANE Select	c.1220-2918T>C		intron	N/A	ENSP00000263063.3
	MTPAP	ENST00000488290.5	TSL:2	n.2975-2918T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85066 AN: 151798 Hom.: 25904 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.560 AC: 85089 AN: 151916 Hom.: 25906 Cov.: 31 AF XY: 0.561 AC XY: 41686 AN XY: 74266

African (AFR) AF: 0.333 AC: 13798 AN: 41392

American (AMR) AF: 0.638 AC: 9732 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1002 AN: 5168

South Asian (SAS) AF: 0.566 AC: 2725 AN: 4814

European-Finnish (FIN) AF: 0.719 AC: 7576 AN: 10532

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46022 AN: 67964

Other (OTH) AF: 0.581 AC: 1225 AN: 2110

Alfa AF: 0.630 Hom.: 3912

Bravo AF: 0.543

Asia WGS AF: 0.372 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs639299; hg19: chr10-30608057;