dbSNP rs12354209: MTR:c.34+215G>A (chr1-236795952-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000254.3(MTR):c.34+215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,086 control chromosomes in the GnomAD database, including 37,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.69 ( 37102 hom., cov: 32)

Consequence

MTR
NM_000254.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.704

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

methylcobalamin deficiency type cblG
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

MTR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-236795952-G-A is Benign according to our data. Variant chr1-236795952-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227726.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTR	NM_000254.3 link	c.34+215G>A		intron_variant	Intron 1 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.34+215G>A		intron_variant	Intron 1 of 32	1	NM_000254.3	ENSP00000355536.5		Q99707-1

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104907

AN:

151968

Hom.:

37037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.837

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.605

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.649

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.691

AC:

105037

AN:

152086

Hom.:

37102

Cov.:

AF XY:

0.692

AC XY:

51427

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.837

AC:

34771

AN:

41520

American (AMR)

AF:

0.658

AC:

10069

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1821

AN:

3470

East Asian (EAS)

AF:

0.606

AC:

3119

AN:

5150

South Asian (SAS)

AF:

0.736

AC:

3554

AN:

4826

European-Finnish (FIN)

AF:

0.649

AC:

6856

AN:

10562

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.627

AC:

42586

AN:

67942

Other (OTH)

AF:

0.650

AC:

1376

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1624

3248

4873

6497

8121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.650

Hom.:

23825

Bravo

AF:

0.695

Asia WGS

AF:

0.685

AC:

2380

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.79

PhyloP100

-0.70

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over