rs10733117

chr1-236800567-G-Achr1-236800567-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.35-2861G>A		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.35-2861G>A		intron_variant		1	NM_000254.3	P1

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

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.638

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.616

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.586

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

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.531

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.49
Dann	Benign	0.29

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: rs10733117; hg19: chr1-236963867;