Variant 4-118691572-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020961.4(METTL14):c.284A>G(p.Tyr95Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,405,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

METTL14
NM_020961.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70

Variant links:

Genes affected

METTL14 (HGNC:29330): (methyltransferase 14, N6-adenosine-methyltransferase subunit) Enables mRNA binding activity. Contributes to mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity. Involved in mRNA metabolic process; negative regulation of hematopoietic progenitor cell differentiation; and positive regulation of translation. Located in nucleoplasm. Part of RNA N6-methyladenosine methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

METTL14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL14	NM_020961.4 linkuse as main transcript	c.284A>G	p.Tyr95Cys	missense_variant	4/11	ENST00000388822.10
METTL14	XM_047416029.1 linkuse as main transcript	c.284A>G	p.Tyr95Cys	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
METTL14	ENST00000388822.10 linkuse as main transcript	c.284A>G	p.Tyr95Cys	missense_variant	4/11	1	NM_020961.4	P1
METTL14	ENST00000502564.2 linkuse as main transcript	n.39A>G		non_coding_transcript_exon_variant	1/4	5
METTL14	ENST00000626212.2 linkuse as main transcript	c.*36A>G		3_prime_UTR_variant, NMD_transcript_variant	4/6	5
METTL14	ENST00000628452.2 linkuse as main transcript	c.*15A>G		3_prime_UTR_variant, NMD_transcript_variant	4/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1405308

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699586

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:

0.00000185

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

Oct 27, 2021

The c.284A>G (p.Y95C) alteration is located in exon 4 (coding exon 4) of the METTL14 gene. This alteration results from a A to G substitution at nucleotide position 284, causing the tyrosine (Y) at amino acid position 95 to be replaced by a cysteine (C). 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

0.071

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0071

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.99

REVEL

Benign

0.18

Sift

Benign

0.15

Sift4G

Benign

0.17

Polyphen

0.91

Vest4

0.62

MutPred

0.25

Gain of glycosylation at Y100 (P = 0.0054);

MVP

0.26

MPC

1.6

ClinPred

0.93

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over