rs12354209

chr1-236795952-G-Achr1-236795952-G-Cchr1-236795952-G-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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.704

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=-0.85).
• BP6: Variant 1-236795952-G-A is Benign according to our data. Variant chr1-236795952-G-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
MTR	NM_000254.3	c.34+215G>A		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.34+215G>A		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104907 AN: 151968 Hom.: 37037 Cov.: 32

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.: 32 AF XY: 0.692 AC XY: 51427 AN XY: 74324

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.650

Alfa AF: 0.651 Hom.: 12246

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

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	-0.85
Cadd	Benign	1.1
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs12354209; hg19: chr1-236959252;