Variant chr6-37435732-C-T 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_015050.3(CMTR1):c.103C>T(p.Pro35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,445,076 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CMTR1
NM_015050.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

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:

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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=0.04733026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CMTR1	NM_015050.3 linkuse as main transcript	c.103C>T	p.Pro35Ser	missense_variant	2/24	ENST00000373451.9	NP_055865.1
CMTR1	XM_047418462.1 linkuse as main transcript	c.103C>T	p.Pro35Ser	missense_variant	3/25		XP_047274418.1
CMTR1	XM_047418463.1 linkuse as main transcript	c.103C>T	p.Pro35Ser	missense_variant	4/26		XP_047274419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CMTR1	ENST00000373451.9 linkuse as main transcript	c.103C>T	p.Pro35Ser	missense_variant	2/24	1	NM_015050.3	ENSP00000362550	P1
CMTR1	ENST00000455891.5 linkuse as main transcript	c.103C>T	p.Pro35Ser	missense_variant	2/10	2		ENSP00000414233
CMTR1	ENST00000471097.1 linkuse as main transcript	n.268C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1445076

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

718722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 19, 2021

The c.103C>T (p.P35S) alteration is located in exon 2 (coding exon 1) of the CMTR1 gene. This alteration results from a C to T substitution at nucleotide position 103, causing the proline (P) at amino acid position 35 to be replaced by a serine (S). 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

0.067

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.024

.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N

MutationTaster

Benign

0.61

PrimateAI

Benign

0.39

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.084

Sift

Benign

0.61

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0

B;B

Vest4

0.17

MutPred

0.27

Gain of phosphorylation at P35 (P = 0.0019);Gain of phosphorylation at P35 (P = 0.0019);

MVP

0.10

MPC

0.041

ClinPred

0.27

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over