Variant 13-102694411-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001010977.3(METTL21C):c.88A>G(p.Lys30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,362 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 Likely benign (★).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

METTL21C
NM_001010977.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.811

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0368461).

BP6

Variant 13-102694411-T-C is Benign according to our data. Variant chr13-102694411-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2529973.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL21C	NM_001010977.3 linkuse as main transcript	c.88A>G	p.Lys30Glu	missense_variant	1/4	ENST00000267273.7
METTL21C	XM_047430117.1 linkuse as main transcript	c.88A>G	p.Lys30Glu	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL21C	ENST00000267273.7 linkuse as main transcript	c.88A>G	p.Lys30Glu	missense_variant	1/4	1	NM_001010977.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249940

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135180

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457362

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725178

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:

0.00000361

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.21

DANN

Benign

0.13

DEOGEN2

Benign

0.00095

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.33

M_CAP

Benign

0.0017

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.060

REVEL

Benign

0.0020

Sift

Benign

0.89

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.10

MutPred

0.22

Gain of loop (P = 0.0013);

MVP

0.34

MPC

0.078

ClinPred

0.029

GERP RS

-1.1

Varity_R

0.048

gMVP

0.34

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