16-722313-C-A

Variant names:

• chr16-722313-C-A
• rs200866589
• NM_023933.3:c.464C>A

Variant summary

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

The NM_023933.3(ANTKMT):​c.464C>A​(p.Pro155Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P155R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078980505).

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.464C>A	p.Pro155Gln	missense	Exon 5 of 5	NP_076422.1	Q9BQD7
	ANTKMT	NM_001271285.2		c.413C>A	p.Pro138Gln	missense	Exon 4 of 4	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.464C>A	p.Pro155Gln	missense	Exon 5 of 5	ENSP00000454380.1	Q9BQD7
	ANTKMT	ENST00000853259.1		c.500C>A	p.Pro167Gln	missense	Exon 5 of 5	ENSP00000523318.1
	ANTKMT	ENST00000853260.1		c.449C>A	p.Pro150Gln	missense	Exon 5 of 5	ENSP00000523319.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455944 Hom.: 0 Cov.: 45 AF XY: 0.00000138 AC XY: 1 AN XY: 723946

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.0000226 AC: 1 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39512

South Asian (SAS) AF: 0.00 AC: 0 AN: 85508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110076

Other (OTH) AF: 0.00 AC: 0 AN: 60106

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.66
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.020
Sift	Benign	0.42	T
Sift4G	Benign	0.43	T
Polyphen		0.047	B
Vest4		0.25
MutPred		0.34		Loss of glycosylation at P155 (P = 0.1243)
MVP		0.11
MPC		0.085
ClinPred		0.10	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs200866589; hg19: chr16-772313; COSMIC: COSV99557444; COSMIC: COSV99557444;