rs10802569

chr1-236892005-G-C

Variant summary

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

The NM_000254.3(MTR):c.3204+676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,942 control chromosomes in the GnomAD database, including 33,554 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 0.66 (33554 hom., cov: 31)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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 (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.3204+676G>C		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.3204+676G>C		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100383 AN: 151824 Hom.: 33513 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.661 AC: 100478 AN: 151942 Hom.: 33554 Cov.: 31 AF XY: 0.663 AC XY: 49250 AN XY: 74266

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.615

Alfa AF: 0.648 Hom.: 3983

Bravo AF: 0.662

Asia WGS AF: 0.666 AC: 2315 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	0.45
Dann	Benign	0.37

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: rs10802569; hg19: chr1-237055305;