Genetic Variant MTR:c.3406-296C>T (chr1-236895062-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000254.3(MTR):c.3406-296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 427,730 control chromosomes in the GnomAD database, including 73,462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24250 hom., cov: 31)

Exomes 𝑓: 0.59 ( 49212 hom. )

Consequence

MTR
NM_000254.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.480

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=-0.88).

BP6

Variant 1-236895062-C-T is Benign according to our data. Variant chr1-236895062-C-T is described in ClinVar as [Benign]. Clinvar id is 1267985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTR	NM_000254.3 link	c.3406-296C>T		intron_variant	Intron 30 of 32	ENST00000366577.10	NP_000245.2	Q99707-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10 link	c.3406-296C>T		intron_variant	Intron 30 of 32	1	NM_000254.3	ENSP00000355536.5		Q99707-1
MTR	ENST00000366576.3 link	c.2068-296C>T		intron_variant	Intron 17 of 19	1		ENSP00000355535.3		B1ANE3

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

84970

AN:

151740

Hom.:

24223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.762

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.528

GnomAD4 exome

AF:

0.593

AC:

163678

AN:

275874

Hom.:

49212

Cov.:

AF XY:

0.596

AC XY:

87751

AN XY:

147316

show subpopulations

Gnomad4 AFR exome

AF:

0.456

Gnomad4 AMR exome

AF:

0.616

Gnomad4 ASJ exome

AF:

0.492

Gnomad4 EAS exome

AF:

0.585

Gnomad4 SAS exome

AF:

0.621

Gnomad4 FIN exome

AF:

0.635

Gnomad4 NFE exome

AF:

0.596

Gnomad4 OTH exome

AF:

0.575

GnomAD4 genome

AF:

0.560

AC:

85038

AN:

151856

Hom.:

24250

Cov.:

AF XY:

0.563

AC XY:

41809

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.551

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.636

Gnomad4 NFE

AF:

0.602

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.581

Hom.:

3220

Bravo

AF:

0.551

Asia WGS

AF:

0.575

AC:

1998

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.14

DANN

Benign

0.68

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