rs775572823

Variant names:

• chr10-30336928-C-A
• NM_018109.4:c.655G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-30336928-C-A
• chr10-30336928-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018109.4(MTPAP):​c.655G>T​(p.Ala219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MTPAP NM_018109.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10155171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTPAP	NM_018109.4	c.655G>T	p.Ala219Ser	missense_variant	Exon 4 of 9	ENST00000263063.9	NP_060579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTPAP	ENST00000263063.9	c.655G>T	p.Ala219Ser	missense_variant	Exon 4 of 9	1	NM_018109.4	ENSP00000263063.3
MTPAP	ENST00000417581.1	c.460G>T	p.Ala154Ser	missense_variant	Exon 4 of 5	5		ENSP00000404392.1
MTPAP	ENST00000488290.5	n.2410G>T		non_coding_transcript_exon_variant	Exon 12 of 17	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461120 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.059
Sift	Benign	0.45	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.016	B;.
Vest4		0.29
MutPred		0.40		Loss of catalytic residue at A219 (P = 0.0457);.;
MVP		0.34
MPC		0.40
ClinPred		0.39	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-30625857;