rs11818836

Variant names:

• chr10-30352205-T-C
• rs11818836
• ENST00000488290.5:n.1913-10565A>G

Variant summary

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

The ENST00000488290.5(MTPAP):​n.1913-10565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,110 control chromosomes in the GnomAD database, including 15,458 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 0.41 (15458 hom., cov: 32)
• Consequence: MTPAP ENST00000488290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• 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: 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 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.1913-10565A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61687 AN: 151990 Hom.: 15455 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.406 AC: 61688 AN: 152110 Hom.: 15458 Cov.: 32 AF XY: 0.405 AC XY: 30098 AN XY: 74340

African (AFR) AF: 0.112 AC: 4636 AN: 41528

American (AMR) AF: 0.526 AC: 8035 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3470

East Asian (EAS) AF: 0.174 AC: 901 AN: 5172

South Asian (SAS) AF: 0.421 AC: 2029 AN: 4814

European-Finnish (FIN) AF: 0.488 AC: 5157 AN: 10558

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37511 AN: 67976

Other (OTH) AF: 0.445 AC: 940 AN: 2114

Alfa AF: 0.514 Hom.: 10692

Bravo AF: 0.397

Asia WGS AF: 0.287 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.0
DANN	Benign	0.94
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11818836; hg19: chr10-30641134;