rs10925250

chr1-236858830-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.1954-1003A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,062 control chromosomes in the GnomAD database, including 3,691 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 0.21 (3691 hom., cov: 32)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.1954-1003A>G		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.1954-1003A>G		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32467 AN: 151944 Hom.: 3680 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.214 AC: 32505 AN: 152062 Hom.: 3691 Cov.: 32 AF XY: 0.215 AC XY: 16004 AN XY: 74348

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.195

Alfa AF: 0.208 Hom.: 384

Bravo AF: 0.210

Asia WGS AF: 0.219 AC: 760 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	0.015
Dann	Benign	0.20

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: rs10925250; hg19: chr1-237022130;