rs12060264

chr1-236825063-G-Achr1-236825063-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000254.3(MTR):c.866-275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,220 control chromosomes in the GnomAD database, including 9,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9735 hom., cov: 30)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-236825063-G-A is Benign according to our data. Variant chr1-236825063-G-A is described in ClinVar as [Benign]. Clinvar id is 1286806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.866-275G>A		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.866-275G>A		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52363 AN: 151130 Hom.: 9736 Cov.: 30

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.314

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.346 AC: 52383 AN: 151220 Hom.: 9735 Cov.: 30 AF XY: 0.346 AC XY: 25577 AN XY: 73832

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.336

Alfa AF: 0.359 Hom.: 4081

Bravo AF: 0.344

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs12060264; hg19: chr1-236988363;