rs10925257

Positions:

• chr1-236882860-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.2676+2024A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,216 control chromosomes in the GnomAD database, including 3,685 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 (3685 hom., cov: 33)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.2676+2024A>G		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.2676+2024A>G		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32398 AN: 152098 Hom.: 3674 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.213 AC: 32435 AN: 152216 Hom.: 3685 Cov.: 33 AF XY: 0.215 AC XY: 15963 AN XY: 74408

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.197

Alfa AF: 0.193 Hom.: 5560

Bravo AF: 0.209

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.17
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10925257; hg19: chr1-237046160;