1-236846557-C-T

Position:

• chr1-236846557-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.1516-3787C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,930 control chromosomes in the GnomAD database, including 14,688 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 0.44 (14688 hom., cov: 33)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.1516-3787C>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.1516-3787C>T		intron_variant		1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.178-3787C>T		intron_variant		1		ENSP00000355535.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66331 AN: 151812 Hom.: 14671 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.437 AC: 66398 AN: 151930 Hom.: 14688 Cov.: 33 AF XY: 0.437 AC XY: 32467 AN XY: 74260

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.430

Alfa AF: 0.313 Hom.: 819

Bravo AF: 0.441

Asia WGS AF: 0.442 AC: 1535 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.081
DANN	Benign	0.43

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: rs3754255; hg19: chr1-237009857;