Variant 18-13731521-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003799.3(RNMT):c.4G>A(p.Ala2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,584,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

RNMT
NM_003799.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

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 made for transcript

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=0.10988784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNMT	NM_003799.3 linkuse as main transcript	c.4G>A	p.Ala2Thr	missense_variant	3/12	ENST00000383314.7	NP_003790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNMT	ENST00000383314.7 linkuse as main transcript	c.4G>A	p.Ala2Thr	missense_variant	3/12	1	NM_003799.3	ENSP00000372804	P1	O43148-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0000655

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:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

229162

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

124564

show subpopulations

Gnomad AFR exome

AF:

0.0000652

Gnomad AMR exome

AF:

0.0000699

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000267

AC:

383

AN:

1432416

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

189

AN XY:

710750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000629

Gnomad4 AMR exome

AF:

0.0000523

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:

0.000336

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000151

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000286

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.4G>A (p.A2T) alteration is located in exon 3 (coding exon 1) of the RNMT gene. This alteration results from a G to A substitution at nucleotide position 4, causing the alanine (A) at amino acid position 2 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.010

T;T;.;T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.30

.;.;T;T;.;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;.;N;N

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.060

N;N;.;.;.;N

REVEL

Benign

0.14

Sift

Benign

0.069

T;T;.;.;.;T

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

0.016

B;B;B;.;B;B

Vest4

0.17

MVP

0.46

MPC

0.22

ClinPred

0.057

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over