rs955516

chr1-236817204-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000254.3(MTR):c.764+661T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,996 control chromosomes in the GnomAD database, including 10,015 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 0.35 (10015 hom., cov: 32)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.764+661T>A		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.764+661T>A		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53068 AN: 151878 Hom.: 10013 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.349 AC: 53101 AN: 151996 Hom.: 10015 Cov.: 32 AF XY: 0.351 AC XY: 26051 AN XY: 74286

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.345

Alfa AF: 0.375 Hom.: 1407

Bravo AF: 0.345

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.66

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: rs955516; hg19: chr1-236980504;