rs796052172

Positions:

• chr19-620430-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM2 PP3_Strong BP6

The NM_005035.4(POLRMT):​c.2698G>A​(p.Glu900Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: POLRMT NM_005035.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.44

Genes affected

POLRMT (HGNC:9200): (RNA polymerase mitochondrial) This gene encodes a mitochondrial DNA-directed RNA polymerase. The gene product is responsible for mitochondrial gene expression as well as for providing RNA primers for initiation of replication of the mitochondrial genome. Although this polypeptide has the same function as the three nuclear DNA-directed RNA polymerases, it is more closely related to RNA polymerases of phage and mitochondrial polymerases of lower eukaryotes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.963
• BP6: Variant 19-620430-C-T is Benign according to our data. Variant chr19-620430-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 207890.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLRMT	NM_005035.4	c.2698G>A	p.Glu900Lys	missense_variant	11/21	ENST00000588649.7	NP_005026.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLRMT	ENST00000588649.7	c.2698G>A	p.Glu900Lys	missense_variant	11/21	1	NM_005035.4	ENSP00000465759	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1446148 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 717770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.0000513

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Pathogenic	4.0	H
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.83		Gain of ubiquitination at E900 (P = 0.0539);
MVP		0.64
MPC		0.84
ClinPred		1.0	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.98
gMVP		0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs796052172; hg19: chr19-620430;