rs201213742

Variant names:

• chr18-2554950-T-A
• rs201213742
• NM_022840.5:c.548A>T

Your query was ambiguous. Multiple possible variants found:

• chr18-2554950-T-A
• chr18-2554950-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022840.5(METTL4):​c.548A>T​(p.Asp183Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D183G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: METTL4 NM_022840.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 0 publications found

Genes affected

METTL4 (HGNC:24726): (methyltransferase 4, N6-adenosine) Enables RNA methyltransferase activity and site-specific DNA-methyltransferase (adenine-specific) activity. Involved in nucleic acid metabolic process; regulation of RNA metabolic process; and regulation of mitochondrial DNA replication. Located in cytosol; mitochondrial matrix; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0826948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL4	NM_022840.5	c.548A>T	p.Asp183Val	missense_variant	Exon 4 of 9	ENST00000574538.2	NP_073751.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL4	ENST00000574538.2	c.548A>T	p.Asp183Val	missense_variant	Exon 4 of 9	1	NM_022840.5	ENSP00000458290.1
METTL4	ENST00000573134.1	n.945A>T		non_coding_transcript_exon_variant	Exon 3 of 7	1
METTL4	ENST00000319888.10	c.548A>T	p.Asp183Val	missense_variant	Exon 4 of 8	5		ENSP00000320349.6
METTL4	ENST00000577166.5	c.107A>T	p.Asp36Val	missense_variant	Exon 4 of 4	4		ENSP00000458415.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0041	.;T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M;.
PhyloP100		0.33
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.033
Sift	Uncertain	0.0080	D;.;.
Sift4G	Benign	0.096	T;T;.
Polyphen		0.017	.;B;.
Vest4		0.27
MutPred		0.34		Loss of disorder (P = 0.0223);Loss of disorder (P = 0.0223);.;
MVP		0.61
MPC		0.15
ClinPred		0.12	T
GERP RS		3.4
PromoterAI		0.0065	Neutral
Varity_R		0.18
gMVP		0.37
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201213742; hg19: chr18-2554949;