17-2420271-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The ENST00000263092.11(METTL16):​c.1388C>A​(p.Thr463Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

METTL16
ENST00000263092.11 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.545
Variant links:
Genes affected
METTL16 (HGNC:28484): (methyltransferase 16, RNA N6-adenosine) Enables RNA binding activity and RNA methyltransferase activity. Involved in RNA modification and regulation of mRNA metabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1
In a modified_residue Phosphothreonine (size 0) in uniprot entity MET16_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.045446366).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
METTL16NM_024086.4 linkuse as main transcriptc.1388C>A p.Thr463Lys missense_variant 10/10 ENST00000263092.11 NP_076991.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
METTL16ENST00000263092.11 linkuse as main transcriptc.1388C>A p.Thr463Lys missense_variant 10/101 NM_024086.4 ENSP00000263092 P1Q86W50-1
METTL16ENST00000571669.6 linkuse as main transcriptn.1393C>A non_coding_transcript_exon_variant 9/95
METTL16ENST00000574752.5 linkuse as main transcriptc.*932C>A 3_prime_UTR_variant, NMD_transcript_variant 10/105 ENSP00000460207
METTL16ENST00000576556.5 linkuse as main transcriptc.*765C>A 3_prime_UTR_variant, NMD_transcript_variant 8/82 ENSP00000460775

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152094
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000221
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000803
AC:
20
AN:
249000
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135176
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000212
AC:
310
AN:
1461462
Hom.:
0
Cov.:
31
AF XY:
0.000177
AC XY:
129
AN XY:
727062
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:
0.000250
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152094
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000671
Hom.:
0
Bravo
AF:
0.000113
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000745
AC:
9
EpiCase
AF:
0.000273
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 01, 2021The c.1388C>A (p.T463K) alteration is located in exon 10 (coding exon 9) of the METTL16 gene. This alteration results from a C to A substitution at nucleotide position 1388, causing the threonine (T) at amino acid position 463 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.54
DANN
Benign
0.84
DEOGEN2
Benign
0.0083
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.045
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.018
Sift
Benign
0.34
T
Sift4G
Benign
0.30
T
Polyphen
0.0010
B
Vest4
0.17
MutPred
0.16
Loss of phosphorylation at T463 (P = 0.0015);
MVP
0.068
MPC
0.35
ClinPred
0.024
T
GERP RS
-0.64
Varity_R
0.022
gMVP
0.24

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: rs199862913; hg19: chr17-2323565; API