rs703842

Variant summary

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

The NM_005371.6(METTL1):​c.*40T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

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]

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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/exons MANE Protein UniProt
METTL1NM_005371.6 linkuse as main transcriptc.*40T>G 3_prime_UTR_variant 6/6 ENST00000324871.12 NP_005362.3 Q9UBP6-1
METTL1NM_023033.4 linkuse as main transcriptc.*218T>G 3_prime_UTR_variant 5/5 NP_075422.3 Q9UBP6-2
METTL1XM_005268873.3 linkuse as main transcriptc.*40T>G 3_prime_UTR_variant 7/7 XP_005268930.1
METTL1XM_047428854.1 linkuse as main transcriptc.*40T>G 3_prime_UTR_variant 5/5 XP_047284810.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
METTL1ENST00000324871 linkuse as main transcriptc.*40T>G 3_prime_UTR_variant 6/61 NM_005371.6 ENSP00000314441.7 Q9UBP6-1
METTL1ENST00000257848 linkuse as main transcriptc.*218T>G 3_prime_UTR_variant 5/51 ENSP00000257848.7 Q9UBP6-2
CYP27B1ENST00000546609.1 linkuse as main transcriptc.29T>G p.Ile10Ser missense_variant 1/45 V9GYP0
METTL1ENST00000547653 linkuse as main transcriptc.*218T>G 3_prime_UTR_variant 3/33 ENSP00000447838.1 H0YHU4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.99e-7
AC:
1
AN:
1430004
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
704924
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.19e-7
Gnomad4 OTH exome
AF:
0.00
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