rs1266164

chr1-236887651-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000254.3(MTR):c.2851+1284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,206 control chromosomes in the GnomAD database, including 7,103 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7103 hom., cov: 34)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.2851+1284C>T		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.2851+1284C>T		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41902 AN: 152088 Hom.: 7109 Cov.: 34

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.275 AC: 41890 AN: 152206 Hom.: 7103 Cov.: 34 AF XY: 0.274 AC XY: 20411 AN XY: 74398

Gnomad4 AFR AF: 0.0817

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.310

Alfa AF: 0.338 Hom.: 2589

Bravo AF: 0.264

Asia WGS AF: 0.228 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.70
Dann	Benign	0.80

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: rs1266164; hg19: chr1-237050951;