rs3776465

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002454.3(MTRR):​c.780+541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,200 control chromosomes in the GnomAD database, including 6,200 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 0.28 ( 6200 hom., cov: 32)

Consequence

MTRR
NM_002454.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.152
Variant links:
Genes affected
MTRR (HGNC:7473): (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTRRNM_002454.3 linkuse as main transcriptc.780+541T>C intron_variant ENST00000440940.7 NP_002445.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTRRENST00000440940.7 linkuse as main transcriptc.780+541T>C intron_variant 1 NM_002454.3 ENSP00000402510 P1Q9UBK8-2

Frequencies

GnomAD3 genomes
AF:
0.279
AC:
42460
AN:
152082
Hom.:
6200
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.237
Gnomad AMI
AF:
0.382
Gnomad AMR
AF:
0.226
Gnomad ASJ
AF:
0.230
Gnomad EAS
AF:
0.188
Gnomad SAS
AF:
0.244
Gnomad FIN
AF:
0.350
Gnomad MID
AF:
0.196
Gnomad NFE
AF:
0.317
Gnomad OTH
AF:
0.268
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.279
AC:
42465
AN:
152200
Hom.:
6200
Cov.:
32
AF XY:
0.279
AC XY:
20746
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.236
Gnomad4 AMR
AF:
0.226
Gnomad4 ASJ
AF:
0.230
Gnomad4 EAS
AF:
0.188
Gnomad4 SAS
AF:
0.243
Gnomad4 FIN
AF:
0.350
Gnomad4 NFE
AF:
0.317
Gnomad4 OTH
AF:
0.265
Alfa
AF:
0.292
Hom.:
883
Bravo
AF:
0.266
Asia WGS
AF:
0.175
AC:
610
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.76
DANN
Benign
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3776465; hg19: chr5-7878976; API