1-236849589-A-G

Position:

• chr1-236849589-A-G

Variant summary

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

The NM_000254.3(MTR):​c.1516-755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,954 control chromosomes in the GnomAD database, including 10,464 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 0.36 (10464 hom., cov: 31)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.1516-755A>G		intron_variant		ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.1516-755A>G		intron_variant		1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.178-755A>G		intron_variant		1		ENSP00000355535.3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54310 AN: 151836 Hom.: 10456 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.358 AC: 54354 AN: 151954 Hom.: 10464 Cov.: 31 AF XY: 0.359 AC XY: 26662 AN XY: 74258

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.356

Alfa AF: 0.383 Hom.: 1455

Bravo AF: 0.353

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.7
DANN	Benign	0.44

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: rs12563688; hg19: chr1-237012889;