rs12060264

Variant names:

• chr1-236825063-G-A
• rs12060264
• NM_000254.3:c.866-275G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-236825063-G-A
• chr1-236825063-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MTR	NM_000254.3	c.866-275G>A		intron_variant	Intron 9 of 32	ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.866-275G>A		intron_variant	Intron 9 of 32	1	NM_000254.3	ENSP00000355536.5

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

African (AFR) AF: 0.206 AC: 8467 AN: 41138

American (AMR) AF: 0.406 AC: 6168 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2104 AN: 5132

South Asian (SAS) AF: 0.293 AC: 1407 AN: 4802

European-Finnish (FIN) AF: 0.400 AC: 4124 AN: 10322

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27774 AN: 67862

Other (OTH) AF: 0.336 AC: 700 AN: 2082

Alfa AF: 0.374 Hom.: 6192

Bravo AF: 0.344

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 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	-0.91
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12060264; hg19: chr1-236988363;