16-722102-C-G

Variant names:

• chr16-722102-C-G
• rs143857437
• NM_023933.3:c.427C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023933.3(ANTKMT):​c.427C>G​(p.Arg143Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R143S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05430311).

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.427C>G	p.Arg143Gly	missense	Exon 4 of 5	NP_076422.1	Q9BQD7
	ANTKMT	NM_001271285.2		c.408+161C>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.427C>G	p.Arg143Gly	missense	Exon 4 of 5	ENSP00000454380.1	Q9BQD7
	ANTKMT	ENST00000853259.1		c.463C>G	p.Arg155Gly	missense	Exon 4 of 5	ENSP00000523318.1
	ANTKMT	ENST00000853261.1		c.322C>G	p.Arg108Gly	missense	Exon 3 of 4	ENSP00000523320.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456164 Hom.: 0 Cov.: 81 AF XY: 0.00 AC XY: 0 AN XY: 724278

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39368

South Asian (SAS) AF: 0.00 AC: 0 AN: 85476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110772

Other (OTH) AF: 0.00 AC: 0 AN: 60160

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
Sift	Benign	0.22	T
Sift4G	Benign	0.40	T
Polyphen		0.040	B
Vest4		0.26
MutPred		0.65		Loss of MoRF binding (P = 0.0228)
MVP		0.10
MPC		0.13
ClinPred		0.085	T
GERP RS		-1.0
PromoterAI		-0.0084	Neutral
Varity_R		0.14
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs143857437; hg19: chr16-772102;