rs6668344

Positions:

• chr1-236838026-C-T

Variant summary

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

The ENST00000366577.10(MTR):​c.1330-388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,914 control chromosomes in the GnomAD database, including 11,109 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 0.38 (11109 hom., cov: 32)
• Consequence: MTR ENST00000366577.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.1330-388C>T		intron_variant		ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.1330-388C>T		intron_variant		1	NM_000254.3	ENSP00000355536	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57011 AN: 151796 Hom.: 11101 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.376 AC: 57055 AN: 151914 Hom.: 11109 Cov.: 32 AF XY: 0.377 AC XY: 27998 AN XY: 74230

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.369

Alfa AF: 0.395 Hom.: 2827

Bravo AF: 0.373

Asia WGS AF: 0.361 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.25

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: rs6668344; hg19: chr1-237001326;