Variant 6-37461588-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_015050.3(CMTR1):c.1135C>T(p.Leu379Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,611,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CMTR1
NM_015050.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71

Variant links:

Genes affected

CMTR1 (HGNC:21077): (cap methyltransferase 1) Enables mRNA (nucleoside-2'-O-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping and cap1 mRNA methylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CMTR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.747

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CMTR1	NM_015050.3 linkuse as main transcript	c.1135C>T	p.Leu379Phe	missense_variant	11/24	ENST00000373451.9	NP_055865.1
CMTR1	XM_047418462.1 linkuse as main transcript	c.1135C>T	p.Leu379Phe	missense_variant	12/25		XP_047274418.1
CMTR1	XM_047418463.1 linkuse as main transcript	c.1135C>T	p.Leu379Phe	missense_variant	13/26		XP_047274419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CMTR1	ENST00000373451.9 linkuse as main transcript	c.1135C>T	p.Leu379Phe	missense_variant	11/24	1	NM_015050.3	ENSP00000362550	P1
CMTR1	ENST00000455891.5 linkuse as main transcript	c.967C>T	p.Leu323Phe	missense_variant	9/10	2		ENSP00000414233
CMTR1	ENST00000493656.1 linkuse as main transcript	n.66C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249524

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459522

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000158

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 03, 2021

The c.1135C>T (p.L379F) alteration is located in exon 11 (coding exon 10) of the CMTR1 gene. This alteration results from a C to T substitution at nucleotide position 1135, causing the leucine (L) at amino acid position 379 to be replaced by a phenylalanine (F). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

.;T

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.75

D;D

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.6

.;H

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.025

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.54

MutPred

0.65

.;Gain of ubiquitination at K381 (P = 0.1446);

MVP

0.57

MPC

2.0

ClinPred

0.97

GERP RS

5.6

Varity_R

0.78

gMVP

0.70

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

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