10-30327945-T-C

Variant names:

• chr10-30327945-T-C
• rs959629
• NM_018109.4:c.781-1310A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.89).
• 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 rank	MANE	Protein	UniProt
MTPAP	NM_018109.4	c.781-1310A>G		intron_variant	Intron 4 of 8	ENST00000263063.9	NP_060579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTPAP	ENST00000263063.9	c.781-1310A>G		intron_variant	Intron 4 of 8	1	NM_018109.4	ENSP00000263063.3
MTPAP	ENST00000417581.1	c.586-1310A>G		intron_variant	Intron 4 of 4	5		ENSP00000404392.1
MTPAP	ENST00000488290.5	n.2536-1310A>G		intron_variant	Intron 12 of 16	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

African (AFR) AF: 0.112 AC: 4656 AN: 41510

American (AMR) AF: 0.523 AC: 7980 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1839 AN: 3464

East Asian (EAS) AF: 0.134 AC: 696 AN: 5178

South Asian (SAS) AF: 0.424 AC: 2044 AN: 4820

European-Finnish (FIN) AF: 0.488 AC: 5144 AN: 10532

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.552 AC: 37485 AN: 67952

Other (OTH) AF: 0.443 AC: 935 AN: 2110

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
PhyloP100		-0.14
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: rs959629; hg19: chr10-30616874;