16-8629088-C-G

Position:

• chr16-8629088-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024109.4(METTL22):​c.492C>G​(p.Ser164Arg) 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. 13/21 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)
• Consequence: METTL22 NM_024109.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.304

Genes affected

METTL22 (HGNC:28368): (methyltransferase 22, Kin17 lysine) This gene encodes a member of the non-histone lysine methyltransferases. It interacts with its substrate, Kin17, which is involved in DNA repair and replication and mRNA processing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

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=0.13129392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL22	NM_024109.4	c.492C>G	p.Ser164Arg	missense_variant	3/11	ENST00000381920.8	NP_077014.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL22	ENST00000381920.8	c.492C>G	p.Ser164Arg	missense_variant	3/11	5	NM_024109.4	ENSP00000371345	P2
METTL22	ENST00000163678.11	c.492C>G	p.Ser164Arg	missense_variant, NMD_transcript_variant	3/10	1		ENSP00000163678
METTL22	ENST00000561758.5	c.324C>G	p.Ser108Arg	missense_variant	4/12	5		ENSP00000457152	A2
METTL22	ENST00000567295.5	c.*178C>G		3_prime_UTR_variant, NMD_transcript_variant	3/5	3		ENSP00000457913

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.492C>G (p.S164R) alteration is located in exon 3 (coding exon 2) of the METTL22 gene. This alteration results from a C to G substitution at nucleotide position 492, causing the serine (S) at amino acid position 164 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0048	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.052
Sift	Uncertain	0.023	D;T
Sift4G	Benign	0.25	T;T
Polyphen		0.94	P;.
Vest4		0.10
MutPred		0.39		Gain of catalytic residue at S164 (P = 0.0028);.;
MVP		0.34
MPC		0.017
ClinPred		0.31	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.085
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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.

Other links and lift over

hg19: chr16-8722945;