rs3768150

Variant names:

• chr1-236889492-T-A
• rs3768150
• NM_000254.3:c.3007+156T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-236889492-T-A
• chr1-236889492-T-C
• chr1-236889492-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000254.3(MTR):​c.3007+156T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,086 control chromosomes in the GnomAD database, including 37,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (37073 hom., cov: 32)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• methylcobalamin deficiency type cblG

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-236889492-T-A is Benign according to our data. Variant chr1-236889492-T-A is described in ClinVar as [Benign]. Clinvar id is 1278175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTR	NM_000254.3	c.3007+156T>A		intron_variant	Intron 28 of 32	ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.3007+156T>A		intron_variant	Intron 28 of 32	1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.1669+156T>A		intron_variant	Intron 15 of 19	1		ENSP00000355535.3

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105108 AN: 151968 Hom.: 37027 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.692 AC: 105216 AN: 152086 Hom.: 37073 Cov.: 32 AF XY: 0.694 AC XY: 51562 AN XY: 74342

African (AFR) AF: 0.811 AC: 33647 AN: 41502

American (AMR) AF: 0.663 AC: 10129 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1769 AN: 3464

East Asian (EAS) AF: 0.816 AC: 4222 AN: 5176

South Asian (SAS) AF: 0.724 AC: 3490 AN: 4818

European-Finnish (FIN) AF: 0.653 AC: 6883 AN: 10548

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42782 AN: 67980

Other (OTH) AF: 0.660 AC: 1396 AN: 2116

Alfa AF: 0.660 Hom.: 3965

Bravo AF: 0.699

Asia WGS AF: 0.765 AC: 2657 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.035
DANN	Benign	0.43
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3768150; hg19: chr1-237052792;