chr16-722102-C-T

Variant names:

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

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.427C>T​(p.Arg143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,608,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000020 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: 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=0.098335505).

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>T	p.Arg143Cys	missense	Exon 4 of 5	NP_076422.1	Q9BQD7
	ANTKMT	NM_001271285.2		c.408+161C>T		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>T	p.Arg143Cys	missense	Exon 4 of 5	ENSP00000454380.1	Q9BQD7
	ANTKMT	ENST00000853259.1		c.463C>T	p.Arg155Cys	missense	Exon 4 of 5	ENSP00000523318.1
	ANTKMT	ENST00000853261.1		c.322C>T	p.Arg108Cys	missense	Exon 3 of 4	ENSP00000523320.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152222 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000210 AC: 5 AN: 237982 AF XY: 0.0000154

Gnomad AFR exome AF: 0.0000669

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000377

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000330 AC: 48 AN: 1456164 Hom.: 0 Cov.: 81 AF XY: 0.0000235 AC XY: 17 AN XY: 724278

African (AFR) AF: 0.0000300 AC: 1 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: 0.0000405 AC: 45 AN: 1110772

Other (OTH) AF: 0.0000332 AC: 2 AN: 60160

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152222 Hom.: 0 Cov.: 35 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N
Sift	Uncertain	0.028	D
Sift4G	Benign	0.070	T
Polyphen		0.96	D
Vest4		0.27
MVP		0.23
MPC		0.36
ClinPred		0.22	T
GERP RS		-1.0
PromoterAI		-0.0068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.51
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;