chr1-236897756-A-T

Variant names:

• chr1-236897756-A-T
• rs2853522
• NM_000254.3:c.*112A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000254.3(MTR):​c.*112A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 899,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: MTR NM_000254.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 17 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.*112A>T		3_prime_UTR	Exon 33 of 33	NP_000245.2
	MTR	NM_001291939.1		c.*112A>T		3_prime_UTR	Exon 32 of 32	NP_001278868.1
	MTR	NM_001410942.1		c.*112A>T		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.*112A>T		3_prime_UTR	Exon 33 of 33	ENSP00000355536.5
	MTR	ENST00000535889.6	TSL:1	c.*112A>T		3_prime_UTR	Exon 32 of 32	ENSP00000441845.1
	MTR	ENST00000366576.3	TSL:1	c.*112A>T		3_prime_UTR	Exon 20 of 20	ENSP00000355535.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151678 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000481

GnomAD4 exome AF: 0.00000134 AC: 1 AN: 748090 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 396436

African (AFR) AF: 0.00 AC: 0 AN: 18770

American (AMR) AF: 0.00 AC: 0 AN: 35614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20764

East Asian (EAS) AF: 0.00 AC: 0 AN: 35482

South Asian (SAS) AF: 0.00 AC: 0 AN: 66258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 490544

Other (OTH) AF: 0.0000273 AC: 1 AN: 36682

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151678 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74040

African (AFR) AF: 0.00 AC: 0 AN: 41236

American (AMR) AF: 0.0000656 AC: 1 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67960

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.00 Hom.: 69331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.36
PhyloP100		-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

Other links and lift over

dbSNP: rs2853522; hg19: chr1-237061056;