Genetic Variant RNMT:p.Ser21Leu (chr18-13731579-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003799.3(RNMT):c.62C>T(p.Ser21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,760 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RNMT
NM_003799.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

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ACMG classification

Classification was made for transcript

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=0.08940753).

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>T	p.Ser21Leu	missense	Exon 3 of 12	NP_003790.1	O43148-1
RNMT	NM_001308263.2		c.62C>T	p.Ser21Leu	missense	Exon 3 of 12	NP_001295192.1	O43148-2
RNMT	NM_001378134.1		c.62C>T	p.Ser21Leu	missense	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>T	p.Ser21Leu	missense	Exon 3 of 12	ENSP00000372804.2	O43148-1
RNMT	ENST00000543302.6	TSL:1	c.62C>T	p.Ser21Leu	missense	Exon 2 of 11	ENSP00000446426.1	O43148-1
RNMT	ENST00000589866.5	TSL:1	c.62C>T	p.Ser21Leu	missense	Exon 2 of 11	ENSP00000466252.1	O43148-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000361

AC:

AN:

249502

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1460558

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726550

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.000181

AC:

AN:

44304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111672

Other (OTH)

AF:

0.0000331

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.000262

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.7

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.74

M_CAP

Benign

0.0029

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-0.48

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.84

REVEL

Benign

0.044

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.032

Polyphen

0.81

Vest4

0.093

MutPred

0.14

Loss of phosphorylation at S21 (P = 0.0308)

MVP

0.32

MPC

0.19

ClinPred

0.18

GERP RS

-0.73

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.13

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over