16-722126-C-G

Variant names:

• chr16-722126-C-G
• rs146878454
• NM_023933.3:c.451C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023933.3(ANTKMT):​c.451C>G​(p.Pro151Ala) 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. 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. P151S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 35)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• Publications: 0 publications found

Genes affected

ANTKMT (HGNC:14152): (adenine nucleotide translocase lysine methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40895304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023933.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTKMT	NM_023933.3	MANE Select	c.451C>G	p.Pro151Ala	missense	Exon 4 of 5	NP_076422.1	Q9BQD7
	ANTKMT	NM_001271285.2		c.409-183C>G		intron	N/A	NP_001258214.1	J3KMW5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTKMT	ENST00000569529.6	TSL:1 MANE Select	c.451C>G	p.Pro151Ala	missense	Exon 4 of 5	ENSP00000454380.1	Q9BQD7
	ANTKMT	ENST00000853259.1		c.487C>G	p.Pro163Ala	missense	Exon 4 of 5	ENSP00000523318.1
	ANTKMT	ENST00000853261.1		c.346C>G	p.Pro116Ala	missense	Exon 3 of 4	ENSP00000523320.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.7	D
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.38		Gain of catalytic residue at P151 (P = 0.1094)
MVP		0.33
MPC		0.44
ClinPred		0.99	D
GERP RS		4.3
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs146878454; hg19: chr16-772126;