12-57768956-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005371.6(METTL1):​c.*40T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

METTL1
NM_005371.6 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77
Variant links:
Genes affected
METTL1 (HGNC:7030): (methyltransferase 1, tRNA methylguanosine) This gene is similar in sequence to the S. cerevisiae YDL201w gene. The gene product contains a conserved S-adenosylmethionine-binding motif and is inactivated by phosphorylation. Alternative splice variants encoding different protein isoforms have been described for this gene. A pseudogene has been identified on chromosome X. [provided by RefSeq, Jul 2008]
CYP27B1 (HGNC:2606): (cytochrome P450 family 27 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene localizes to the inner mitochondrial membrane where it hydroxylates 25-hydroxyvitamin D3 at the 1alpha position. This reaction synthesizes 1alpha,25-dihydroxyvitamin D3, the active form of vitamin D3, which binds to the vitamin D receptor and regulates calcium metabolism. Thus this enzyme regulates the level of biologically active vitamin D and plays an important role in calcium homeostasis. Mutations in this gene can result in vitamin D-dependent rickets type I. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
METTL1NM_005371.6 linkc.*40T>A 3_prime_UTR_variant Exon 6 of 6 ENST00000324871.12 NP_005362.3 Q9UBP6-1
METTL1NM_023033.4 linkc.*218T>A 3_prime_UTR_variant Exon 5 of 5 NP_075422.3 Q9UBP6-2
METTL1XM_005268873.3 linkc.*40T>A 3_prime_UTR_variant Exon 7 of 7 XP_005268930.1
METTL1XM_047428854.1 linkc.*40T>A 3_prime_UTR_variant Exon 5 of 5 XP_047284810.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
METTL1ENST00000324871 linkc.*40T>A 3_prime_UTR_variant Exon 6 of 6 1 NM_005371.6 ENSP00000314441.7 Q9UBP6-1
METTL1ENST00000257848 linkc.*218T>A 3_prime_UTR_variant Exon 5 of 5 1 ENSP00000257848.7 Q9UBP6-2
CYP27B1ENST00000546609.1 linkc.29T>A p.Ile10Asn missense_variant Exon 1 of 4 5 V9GYP0
METTL1ENST00000547653 linkc.*218T>A 3_prime_UTR_variant Exon 3 of 3 3 ENSP00000447838.1 H0YHU4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
9.6
DANN
Benign
0.82

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: rs703842; hg19: chr12-58162739; API