rs10495387

Positions:

• chr1-236873957-C-A
• chr1-236873957-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000254.3(MTR):​c.2473+117C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 997,328 control chromosomes in the GnomAD database, including 1,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (773 hom., cov: 32)
  • Exomes 𝑓: 0.032 (967 hom.)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-236873957-C-A is Benign according to our data. Variant chr1-236873957-C-A is described in ClinVar as [Benign]. Clinvar id is 1229463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.2473+117C>A		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.2473+117C>A		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10903 AN: 152048 Hom.: 770 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0666

GnomAD4 exome AF: 0.0318 AC: 26916 AN: 845162 Hom.: 967 AF XY: 0.0332 AC XY: 14595 AN XY: 439080

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.0584

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.0169

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0388

GnomAD4 genome AF: 0.0718 AC: 10923 AN: 152166 Hom.: 773 Cov.: 32 AF XY: 0.0714 AC XY: 5316 AN XY: 74408

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.0896

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0396 Hom.: 79

Bravo AF: 0.0791

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.31
DANN	Benign	0.55

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: rs10495387; hg19: chr1-237037257;