Genetic Variant RNMT:p.Ser21* (chr18-13731579-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_003799.3(RNMT):c.62C>G(p.Ser21*) variant causes a stop gained 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

RNMT
NM_003799.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.482

Publications

0 publications found

Variant links:

Genes affected

RNMT (HGNC:10075): (RNA guanine-7 methyltransferase) Enables RNA binding activity and mRNA (guanine-N7-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping. Located in fibrillar center and nucleoplasm. Part of mRNA cap binding activity complex; mRNA cap methyltransferase complex; and receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

RNMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003799.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNMT	NM_003799.3	MANE Select	c.62C>G	p.Ser21*	stop_gained	Exon 3 of 12	NP_003790.1	O43148-1
RNMT	NM_001308263.2		c.62C>G	p.Ser21*	stop_gained	Exon 3 of 12	NP_001295192.1	O43148-2
RNMT	NM_001378134.1		c.62C>G	p.Ser21*	stop_gained	Exon 2 of 11	NP_001365063.1	O43148-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNMT	ENST00000383314.7	TSL:1 MANE Select	c.62C>G	p.Ser21*	stop_gained	Exon 3 of 12	ENSP00000372804.2	O43148-1
RNMT	ENST00000543302.6	TSL:1	c.62C>G	p.Ser21*	stop_gained	Exon 2 of 11	ENSP00000446426.1	O43148-1
RNMT	ENST00000589866.5	TSL:1	c.62C>G	p.Ser21*	stop_gained	Exon 2 of 11	ENSP00000466252.1	O43148-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Benign

0.11

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.055

PhyloP100

-0.48

Vest4

0.30

GERP RS

-0.73

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=12/188

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.59

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.59

Position offset: -3

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over