rs2275568

Variant names:

• chr1-236852328-C-T
• rs2275568
• NM_000254.3:c.1696-193C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-236852328-C-T
• chr1-236852328-C-A
• chr1-236852328-C-G

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.1696-193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,666 control chromosomes in the GnomAD database, including 13,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (13924 hom., cov: 30)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0500
• 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, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-236852328-C-T is Benign according to our data. Variant chr1-236852328-C-T is described in ClinVar as Benign. ClinVar VariationId is 1262193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000254.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	NM_000254.3	MANE Select	c.1696-193C>T		intron	N/A	NP_000245.2	Q99707-1
	MTR	NM_001291939.1		c.1696-193C>T		intron	N/A	NP_001278868.1	Q99707-2
	MTR	NM_001410942.1		c.1696-193C>T		intron	N/A	NP_001397871.1	A0A7P0TAJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	ENST00000366577.10	TSL:1 MANE Select	c.1696-193C>T		intron	N/A	ENSP00000355536.5	Q99707-1
	MTR	ENST00000535889.6	TSL:1	c.1696-193C>T		intron	N/A	ENSP00000441845.1	Q99707-2
	MTR	ENST00000366576.3	TSL:1	c.358-193C>T		intron	N/A	ENSP00000355535.3	B1ANE3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64501 AN: 151548 Hom.: 13917 Cov.: 30

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.426 AC: 64548 AN: 151666 Hom.: 13924 Cov.: 30 AF XY: 0.426 AC XY: 31523 AN XY: 74084

African (AFR) AF: 0.405 AC: 16725 AN: 41312

American (AMR) AF: 0.456 AC: 6938 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3466

East Asian (EAS) AF: 0.460 AC: 2366 AN: 5148

South Asian (SAS) AF: 0.384 AC: 1845 AN: 4800

European-Finnish (FIN) AF: 0.450 AC: 4715 AN: 10482

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29342 AN: 67930

Other (OTH) AF: 0.417 AC: 877 AN: 2102

Alfa AF: 0.425 Hom.: 43048

Bravo AF: 0.430

Asia WGS AF: 0.426 AC: 1482 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.48
DANN	Benign	0.83
PhyloP100		0.050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2275568;

hg19: chr1-237015628;