Variant chr13-102686044-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010977.3(METTL21C):c.782T>G(p.Leu261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,425,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

METTL21C
NM_001010977.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

METTL21C (HGNC:33717): (methyltransferase 21C, AARS1 lysine) Enables heat shock protein binding activity and protein-lysine N-methyltransferase activity. Involved in protein methylation. Located in nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

METTL21C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10932925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL21C	NM_001010977.3 linkuse as main transcript	c.782T>G	p.Leu261Arg	missense_variant	4/4	ENST00000267273.7
METTL21C	XM_047430117.1 linkuse as main transcript	c.782T>G	p.Leu261Arg	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL21C	ENST00000267273.7 linkuse as main transcript	c.782T>G	p.Leu261Arg	missense_variant	4/4	1	NM_001010977.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000873

AC:

AN:

229016

Hom.:

AF XY:

0.00000813

AC XY:

AN XY:

123032

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1425384

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.782T>G (p.L261R) alteration is located in exon 4 (coding exon 4) of the METTL21C gene. This alteration results from a T to G substitution at nucleotide position 782, causing the leucine (L) at amino acid position 261 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0012

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.67

M_CAP

Benign

0.0078

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.60

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.99

REVEL

Benign

0.025

Sift

Benign

0.11

Sift4G

Benign

0.84

Polyphen

0.0020

Vest4

0.41

MutPred

0.44

Gain of disorder (P = 0.0193);

MVP

0.27

MPC

0.42

ClinPred

0.051

GERP RS

1.8

Varity_R

0.15

gMVP

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over