10-30313631-C-G

Variant names:

• chr10-30313631-C-G
• NM_018109.4:c.1727G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018109.4(MTPAP):​c.1727G>C​(p.Arg576Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTPAP NM_018109.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0580
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08919221).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTPAP	NM_018109.4	MANE Select	c.1727G>C	p.Arg576Thr	missense	Exon 9 of 9	NP_060579.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTPAP	ENST00000263063.9	TSL:1 MANE Select	c.1727G>C	p.Arg576Thr	missense	Exon 9 of 9	ENSP00000263063.3	Q9NVV4-1
	MTPAP	ENST00000958694.1		c.1778G>C	p.Arg593Thr	missense	Exon 10 of 10	ENSP00000628753.1
	MTPAP	ENST00000904049.1		c.1721G>C	p.Arg574Thr	missense	Exon 9 of 9	ENSP00000574108.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.1
DANN	Benign	0.56
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.058
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.11
Sift	Uncertain	0.013	D
Sift4G	Benign	0.11	T
Polyphen		0.50	P
Vest4		0.096
MutPred		0.30		Loss of MoRF binding (P = 0.0016)
MVP		0.27
MPC		0.54
ClinPred		0.16	T
GERP RS		3.8
Varity_R		0.042
gMVP		0.31
Mutation Taster		=91/9	polymorphism

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

hg19: chr10-30602560;