1-236863924-T-C

Position:

• chr1-236863924-T-C

Variant summary

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

The NM_000254.3(MTR):​c.2405+370T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,878 control chromosomes in the GnomAD database, including 40,597 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 0.72 (40597 hom., cov: 29)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.2405+370T>C		intron_variant		ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.2405+370T>C		intron_variant		1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.1067+370T>C		intron_variant		1		ENSP00000355535.3

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109288 AN: 151762 Hom.: 40547 Cov.: 29

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.720 AC: 109400 AN: 151878 Hom.: 40597 Cov.: 29 AF XY: 0.721 AC XY: 53492 AN XY: 74194

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.686

Alfa AF: 0.659 Hom.: 7918

Bravo AF: 0.731

Asia WGS AF: 0.771 AC: 2679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2297967; hg19: chr1-237027224;