1-236849220-G-C

Position:

• chr1-236849220-G-C

Variant summary

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

The NM_000254.3(MTR):​c.1516-1124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,150 control chromosomes in the GnomAD database, including 1,942 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 0.16 (1942 hom., cov: 32)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.1516-1124G>C		intron_variant		ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.1516-1124G>C		intron_variant		1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.178-1124G>C		intron_variant		1		ENSP00000355535.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23651 AN: 152032 Hom.: 1943 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.156 AC: 23661 AN: 152150 Hom.: 1942 Cov.: 32 AF XY: 0.156 AC XY: 11588 AN XY: 74378

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.143

Alfa AF: 0.171 Hom.: 267

Bravo AF: 0.147

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.69
DANN	Benign	0.71

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: rs4659730; hg19: chr1-237012520;