Variant 1-236795637-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000254.3(MTR):c.-67C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,608,430 control chromosomes in the GnomAD database, including 789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 89 hom., cov: 33)

Exomes 𝑓: 0.022 ( 700 hom. )

Consequence

MTR
NM_000254.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.740

Variant links:

Genes affected

MTR (HGNC:7468): (5-methyltetrahydrofolate-homocysteine methyltransferase) This gene encodes the 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

MTR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-236795637-C-T is Benign according to our data. Variant chr1-236795637-C-T is described in ClinVar as [Benign]. Clinvar id is 296545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3 linkuse as main transcript	c.-67C>T		5_prime_UTR_variant	1/33	ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10 linkuse as main transcript	c.-67C>T		5_prime_UTR_variant	1/33	1	NM_000254.3	ENSP00000355536	P1	Q99707-1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4555

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.0655

Gnomad SAS

AF:

0.0881

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0315

AC:

7617

AN:

241504

Hom.:

190

AF XY:

0.0329

AC XY:

4338

AN XY:

131980

show subpopulations

Gnomad AFR exome

AF:

0.0452

Gnomad AMR exome

AF:

0.0275

Gnomad ASJ exome

AF:

0.00950

Gnomad EAS exome

AF:

0.0658

Gnomad SAS exome

AF:

0.0757

Gnomad FIN exome

AF:

0.0169

Gnomad NFE exome

AF:

0.0176

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0224

AC:

32577

AN:

1456086

Hom.:

700

Cov.:

AF XY:

0.0241

AC XY:

17443

AN XY:

724450

show subpopulations

Gnomad4 AFR exome

AF:

0.0466

Gnomad4 AMR exome

AF:

0.0281

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.0711

Gnomad4 SAS exome

AF:

0.0767

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.0158

Gnomad4 OTH exome

AF:

0.0245

GnomAD4 genome

AF:

0.0299

AC:

4556

AN:

152344

Hom.:

Cov.:

AF XY:

0.0310

AC XY:

2308

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.0657

Gnomad4 SAS

AF:

0.0877

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0345

Alfa

AF:

0.0200

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.0770

AC:

267

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 03, 2019	- -

Disorders of Intracellular Cobalamin Metabolism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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