rs3768160

Variant names:

• chr1-236899132-T-C
• rs3768160
• NM_000254.3:c.*1488T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-236899132-T-C
• chr1-236899132-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000254.3(MTR):​c.*1488T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 152,268 control chromosomes in the GnomAD database, including 864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (864 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: MTR NM_000254.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0610
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-236899132-T-C is Benign according to our data. Variant chr1-236899132-T-C is described in ClinVar as Benign. ClinVar VariationId is 296615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000254.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	NM_000254.3	MANE Select	c.*1488T>C		3_prime_UTR	Exon 33 of 33	NP_000245.2
	MTR	NM_001291939.1		c.*1488T>C		3_prime_UTR	Exon 32 of 32	NP_001278868.1
	MTR	NM_001410942.1		c.*1488T>C		3_prime_UTR	Exon 31 of 31	NP_001397871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	ENST00000366577.10	TSL:1 MANE Select	c.*1488T>C		3_prime_UTR	Exon 33 of 33	ENSP00000355536.5
	MTR	ENST00000366576.3	TSL:1	c.*1488T>C		3_prime_UTR	Exon 20 of 20	ENSP00000355535.3
	MTR	ENST00000470570.2	TSL:2	n.6016T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9645 AN: 152150 Hom.: 862 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00397

Gnomad OTH AF: 0.0630

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0635 AC: 9667 AN: 152268 Hom.: 864 Cov.: 33 AF XY: 0.0622 AC XY: 4633 AN XY: 74462

African (AFR) AF: 0.183 AC: 7616 AN: 41512

American (AMR) AF: 0.0289 AC: 443 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1039 AN: 5176

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00397 AC: 270 AN: 68028

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0265 Hom.: 174

Bravo AF: 0.0741

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Disorders of Intracellular Cobalamin Metabolism (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.49
PhyloP100		0.061
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: rs3768160; hg19: chr1-237062432;