rs10925238

chr1-236818623-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.764+2080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,028 control chromosomes in the GnomAD database, including 9,927 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 0.35 (9927 hom., cov: 33)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.764+2080C>T		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.764+2080C>T		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52851 AN: 151908 Hom.: 9924 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.348 AC: 52886 AN: 152028 Hom.: 9927 Cov.: 33 AF XY: 0.349 AC XY: 25962 AN XY: 74316

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.343

Alfa AF: 0.373 Hom.: 1391

Bravo AF: 0.343

Asia WGS AF: 0.347 AC: 1206 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.044
Dann	Benign	0.93

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: rs10925238; hg19: chr1-236981923;