rs10925260

Positions:

• chr1-236884786-A-C

Variant summary

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

The NM_000254.3(MTR):​c.2677-335A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 150,646 control chromosomes in the GnomAD database, including 23,795 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 0.56 (23795 hom., cov: 31)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.2677-335A>C		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.2677-335A>C		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84312 AN: 150528 Hom.: 23768 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.560 AC: 84380 AN: 150646 Hom.: 23795 Cov.: 31 AF XY: 0.564 AC XY: 41467 AN XY: 73580

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.537

Alfa AF: 0.187 Hom.: 548

Bravo AF: 0.548

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.75

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: rs10925260; hg19: chr1-237048086;