1-236852328-C-T

Position:

• chr1-236852328-C-T

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.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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.1696-193C>T		intron_variant		ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.1696-193C>T		intron_variant		1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.358-193C>T		intron_variant		1		ENSP00000355535.3

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

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.417

Alfa AF: 0.423 Hom.: 27967

Bravo AF: 0.430

Asia WGS AF: 0.426 AC: 1482 AN: 3478

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 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

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: rs2275568; hg19: chr1-237015628;