1-236896158-G-C

Position:

• chr1-236896158-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.3598+608G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,072 control chromosomes in the GnomAD database, including 9,942 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 0.35 (9942 hom., cov: 34)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.3598+608G>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.3598+608G>C		intron_variant		1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.2260+608G>C		intron_variant		1		ENSP00000355535.3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52684 AN: 151950 Hom.: 9940 Cov.: 34

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.347 AC: 52708 AN: 152072 Hom.: 9942 Cov.: 34 AF XY: 0.348 AC XY: 25894 AN XY: 74328

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.339

Alfa AF: 0.374 Hom.: 1391

Bravo AF: 0.341

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.5
DANN	Benign	0.62

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: rs4659744; hg19: chr1-237059458;