chr1-236858830-A-G

Variant names:

• chr1-236858830-A-G
• rs10925250
• NM_000254.3:c.1954-1003A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

MTR Gene-Disease associations (from GenCC):

• methylcobalamin deficiency type cblG

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTR	NM_000254.3	c.1954-1003A>G		intron_variant	Intron 18 of 32	ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.1954-1003A>G		intron_variant	Intron 18 of 32	1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.616-1003A>G		intron_variant	Intron 5 of 19	1		ENSP00000355535.3

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

African (AFR) AF: 0.264 AC: 10952 AN: 41470

American (AMR) AF: 0.183 AC: 2799 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3468

East Asian (EAS) AF: 0.119 AC: 618 AN: 5180

South Asian (SAS) AF: 0.311 AC: 1500 AN: 4824

European-Finnish (FIN) AF: 0.190 AC: 2006 AN: 10572

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13377 AN: 67966

Other (OTH) AF: 0.195 AC: 412 AN: 2110

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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10925250; hg19: chr1-237022130;