rs2282369

chr1-236891499-A-Gchr1-236891499-A-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.3204+170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,058 control chromosomes in the GnomAD database, including 35,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35858 hom., cov: 32)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81

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=-0.86).
• BP6: Variant 1-236891499-A-G is Benign according to our data. Variant chr1-236891499-A-G is described in ClinVar as [Benign]. Clinvar id is 1235800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.3204+170A>G		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.3204+170A>G		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103069 AN: 151940 Hom.: 35812 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.679 AC: 103180 AN: 152058 Hom.: 35858 Cov.: 32 AF XY: 0.679 AC XY: 50424 AN XY: 74312

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.641

Alfa AF: 0.656 Hom.: 5223

Bravo AF: 0.688

Asia WGS AF: 0.696 AC: 2417 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

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.13
Dann	Benign	0.21

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: rs2282369; hg19: chr1-237054799;