Variant rs11799670 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.*153A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 702,588 control chromosomes in the GnomAD database, including 1,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 951 hom., cov: 31)

Exomes 𝑓: 0.037 ( 1009 hom. )

Consequence

MTR
NM_000254.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.590

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=-0.87).

BP6

Variant 1-236897797-A-G is Benign according to our data. Variant chr1-236897797-A-G is described in ClinVar as [Benign]. Clinvar id is 296588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3 link	c.*153A>G		3_prime_UTR_variant	33/33	ENST00000366577.10	NP_000245.2	Q99707-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10 link	c.*153A>G		3_prime_UTR_variant	33/33	1	NM_000254.3	ENSP00000355536.5		Q99707-1
MTR	ENST00000366576.3 link	c.*153A>G		3_prime_UTR_variant	20/20	1		ENSP00000355535.3		B1ANE3

Frequencies

GnomAD3 genomes

AF:

0.0760

AC:

11557

AN:

152022

Hom.:

946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0639

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0405

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0594

GnomAD4 exome

AF:

0.0372

AC:

20452

AN:

550444

Hom.:

1009

Cov.:

AF XY:

0.0401

AC XY:

11877

AN XY:

296240

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0583

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.0645

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0448

GnomAD4 genome

AF:

0.0762

AC:

11592

AN:

152144

Hom.:

951

Cov.:

AF XY:

0.0772

AC XY:

5742

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0643

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.0400

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.0634

Alfa

AF:

0.0309

Hom.:

281

Bravo

AF:

0.0833

Asia WGS

AF:

0.0920

AC:

320

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	Jul 05, 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

-0.87

CADD

Benign

0.34

DANN

Benign

0.39

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