rs10733117

Variant names:

• chr1-236800567-G-A
• rs10733117
• NM_000254.3:c.35-2861G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-236800567-G-A
• chr1-236800567-G-C
• chr1-236800567-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000254.3(MTR):​c.35-2861G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 830,534 control chromosomes in the GnomAD database, including 146,979 homozygotes. 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 0.56 (24021 hom., cov: 32)
  • Exomes 𝑓: 0.60 (122958 hom.)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 8 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, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	NM_000254.3	MANE Select	c.35-2861G>A		intron	N/A	NP_000245.2	Q99707-1
	MTR	NM_001291939.1		c.35-2861G>A		intron	N/A	NP_001278868.1	Q99707-2
	MTR	NM_001410942.1		c.35-2861G>A		intron	N/A	NP_001397871.1	A0A7P0TAJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	ENST00000366577.10	TSL:1 MANE Select	c.35-2861G>A		intron	N/A	ENSP00000355536.5	Q99707-1
	MTR	ENST00000535889.6	TSL:1	c.35-2861G>A		intron	N/A	ENSP00000441845.1	Q99707-2
	MTR	ENST00000681102.1		c.35-2861G>A		intron	N/A	ENSP00000505600.1	A0A7P0T9G7

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84432 AN: 151816 Hom.: 23996 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.599 AC: 406761 AN: 678600 Hom.: 122958 AF XY: 0.600 AC XY: 189432 AN XY: 315890

African (AFR) AF: 0.449 AC: 5638 AN: 12570

American (AMR) AF: 0.638 AC: 509 AN: 798

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 2088 AN: 4216

East Asian (EAS) AF: 0.535 AC: 1559 AN: 2912

South Asian (SAS) AF: 0.630 AC: 8445 AN: 13398

European-Finnish (FIN) AF: 0.616 AC: 133 AN: 216

Middle Eastern (MID) AF: 0.513 AC: 693 AN: 1350

European-Non Finnish (NFE) AF: 0.603 AC: 374680 AN: 620938

Other (OTH) AF: 0.586 AC: 13016 AN: 22202

GnomAD4 genome AF: 0.556 AC: 84500 AN: 151934 Hom.: 24021 Cov.: 32 AF XY: 0.560 AC XY: 41550 AN XY: 74260

African (AFR) AF: 0.449 AC: 18560 AN: 41376

American (AMR) AF: 0.582 AC: 8903 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3470

East Asian (EAS) AF: 0.551 AC: 2844 AN: 5164

South Asian (SAS) AF: 0.618 AC: 2982 AN: 4824

European-Finnish (FIN) AF: 0.633 AC: 6666 AN: 10538

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40879 AN: 67962

Other (OTH) AF: 0.531 AC: 1120 AN: 2110

Alfa AF: 0.577 Hom.: 4894

Bravo AF: 0.546

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.29
PhyloP100		-0.60
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: rs10733117; hg19: chr1-236963867;