Variant 16-71284783-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_018348.6(CMTR2):c.1138C>T(p.Arg380Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CMTR2
NM_018348.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

CMTR2 (HGNC:25635): (cap methyltransferase 2) Enables mRNA (nucleoside-2'-O-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping and cap2 mRNA methylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CMTR2 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=0.22250077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTR2	NM_018348.6 linkuse as main transcript	c.1138C>T	p.Arg380Cys	missense_variant	3/3	ENST00000434935.7	NP_060818.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTR2	ENST00000434935.7 linkuse as main transcript	c.1138C>T	p.Arg380Cys	missense_variant	3/3	1	NM_018348.6	ENSP00000411148	P1
CMTR2	ENST00000338099.9 linkuse as main transcript	c.1138C>T	p.Arg380Cys	missense_variant	3/3	1		ENSP00000337512	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247782

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134522

show subpopulations

Gnomad AFR exome

AF:

0.0000642

Gnomad AMR exome

AF:

0.00

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:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

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

Mar 30, 2024

The c.1138C>T (p.R380C) alteration is located in exon 3 (coding exon 1) of the CMTR2 gene. This alteration results from a C to T substitution at nucleotide position 1138, causing the arginine (R) at amino acid position 380 to be replaced by a cysteine (C). 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

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.043

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

.;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.097

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.15

B;B

Vest4

0.25

MutPred

0.52

Gain of catalytic residue at L381 (P = 0.0084);Gain of catalytic residue at L381 (P = 0.0084);

MVP

0.40

MPC

0.057

ClinPred

0.80

GERP RS

5.0

Varity_R

0.19

gMVP

0.50

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