chr5-7900519-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002454.3(MTRR):c.*461T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 169,972 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.016 ( 33 hom., cov: 33)
Exomes 𝑓: 0.015 ( 2 hom. )
Consequence
MTRR
NM_002454.3 3_prime_UTR
NM_002454.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.41
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 5-7900519-T-C is Benign according to our data. Variant chr5-7900519-T-C is described in ClinVar as [Benign]. Clinvar id is 904711.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0165 (2510/152358) while in subpopulation NFE AF= 0.0253 (1718/68030). AF 95% confidence interval is 0.0243. There are 33 homozygotes in gnomad4. There are 1196 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTRR | NM_002454.3 | c.*461T>C | 3_prime_UTR_variant | 15/15 | ENST00000440940.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTRR | ENST00000440940.7 | c.*461T>C | 3_prime_UTR_variant | 15/15 | 1 | NM_002454.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0165 AC: 2509AN: 152240Hom.: 33 Cov.: 33
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GnomAD4 exome AF: 0.0149 AC: 262AN: 17614Hom.: 2 Cov.: 0 AF XY: 0.0146 AC XY: 135AN XY: 9232
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GnomAD4 genome AF: 0.0165 AC: 2510AN: 152358Hom.: 33 Cov.: 33 AF XY: 0.0161 AC XY: 1196AN XY: 74512
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Disorders of Intracellular Cobalamin Metabolism Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at