rs12759827

chr1-236808886-A-G

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.409+113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 860,214 control chromosomes in the GnomAD database, including 24,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3384 hom., cov: 32)
  • Exomes 𝑓: 0.23 (20796 hom.)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.550

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=-0.85).
• BP6: Variant 1-236808886-A-G is Benign according to our data. Variant chr1-236808886-A-G is described in ClinVar as [Benign]. Clinvar id is 1232929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.409+113A>G		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.409+113A>G		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27790 AN: 152044 Hom.: 3384 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.226 AC: 159786 AN: 708052 Hom.: 20796 AF XY: 0.222 AC XY: 83650 AN XY: 377180

Gnomad4 AFR exome AF: 0.0482

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.000472

Gnomad4 SAS exome AF: 0.0821

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.183 AC: 27784 AN: 152162 Hom.: 3384 Cov.: 32 AF XY: 0.176 AC XY: 13098 AN XY: 74410

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0626

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.216

Alfa AF: 0.237 Hom.: 1327

Bravo AF: 0.179

Asia WGS AF: 0.0440 AC: 156 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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.0
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12759827; hg19: chr1-236972186;