Genetic Variant NM_003799.3:c.397G>A (chr18-13731914-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003799.3(RNMT):c.397G>A(p.Asp133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000816 in 1,593,236 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RNMT
NM_003799.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10256946).

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.397G>A	p.Asp133Asn	missense	Exon 3 of 12	NP_003790.1	O43148-1
RNMT	NM_001308263.2		c.397G>A	p.Asp133Asn	missense	Exon 3 of 12	NP_001295192.1	O43148-2
RNMT	NM_001378134.1		c.397G>A	p.Asp133Asn	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.397G>A	p.Asp133Asn	missense	Exon 3 of 12	ENSP00000372804.2	O43148-1
RNMT	ENST00000543302.6	TSL:1	c.397G>A	p.Asp133Asn	missense	Exon 2 of 11	ENSP00000446426.1	O43148-1
RNMT	ENST00000589866.5	TSL:1	c.397G>A	p.Asp133Asn	missense	Exon 2 of 11	ENSP00000466252.1	O43148-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00000873

AC:

AN:

228990

AF XY:

0.00000801

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1441054

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

716482

show subpopulations

African (AFR)

AF:

0.0000629

AC:

AN:

31794

American (AMR)

AF:

0.00

AC:

AN:

38658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.0000244

AC:

AN:

82128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106674

Other (OTH)

AF:

0.00

AC:

AN:

59398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000591

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000330

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

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

0.067

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

0.061

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.64

M_CAP

Benign

0.0046

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.90

PhyloP100

3.4

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.66

REVEL

Benign

0.095

Sift

Benign

0.094

Sift4G

Benign

0.13

Polyphen

0.87

Vest4

0.20

MVP

0.46

MPC

0.21

ClinPred

0.20

GERP RS

4.6

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.035

gMVP

0.24

Mutation Taster

=86/14

polymorphism

(source)

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

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