rs10925252

chr1-236859062-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.1954-771T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,188 control chromosomes in the GnomAD database, including 10,199 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 (10199 hom., cov: 33)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.921

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.1954-771T>C		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.1954-771T>C		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53465 AN: 152068 Hom.: 10194 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.352 AC: 53497 AN: 152188 Hom.: 10199 Cov.: 33 AF XY: 0.353 AC XY: 26268 AN XY: 74410

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.349

Alfa AF: 0.377 Hom.: 1408

Bravo AF: 0.347

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.2
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: rs10925252; hg19: chr1-237022362;