Variant 16-71284758-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018348.6(CMTR2):c.1163C>T(p.Ala388Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,232 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CMTR2
NM_018348.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0310

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028744698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTR2	NM_018348.6 linkuse as main transcript	c.1163C>T	p.Ala388Val	missense_variant	3/3	ENST00000434935.7	NP_060818.4	Q8IYT2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTR2	ENST00000434935.7 linkuse as main transcript	c.1163C>T	p.Ala388Val	missense_variant	3/3	1	NM_018348.6	ENSP00000411148.2		Q8IYT2
CMTR2	ENST00000338099.9 linkuse as main transcript	c.1163C>T	p.Ala388Val	missense_variant	3/3	1		ENSP00000337512.5		Q8IYT2

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247190

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

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

Jan 10, 2023

The c.1163C>T (p.A388V) 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 1163, causing the alanine (A) at amino acid position 388 to be replaced by a valine (V). 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

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.44

DANN

Benign

0.73

DEOGEN2

Benign

0.0059

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.010

Sift

Benign

0.27

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0020

B;B

Vest4

0.030

MutPred

0.32

Gain of methylation at K387 (P = 0.0383);Gain of methylation at K387 (P = 0.0383);

MVP

0.061

MPC

0.043

ClinPred

0.026

GERP RS

-5.0

Varity_R

0.016

gMVP

0.18

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