chr16-721300-C-T

Variant names:

• chr16-721300-C-T
• NM_023933.3:c.26C>T

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.26C>T​(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000084 in 1,191,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0870
• 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=0.026326388).

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.26C>T	p.Ala9Val	missense	Exon 1 of 5	NP_076422.1	Q9BQD7
	ANTKMT	NM_001271285.2		c.26C>T	p.Ala9Val	missense	Exon 1 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.26C>T	p.Ala9Val	missense	Exon 1 of 5	ENSP00000454380.1	Q9BQD7
	ANTKMT	ENST00000853259.1		c.26C>T	p.Ala9Val	missense	Exon 1 of 5	ENSP00000523318.1
	ANTKMT	ENST00000853260.1		c.26C>T	p.Ala9Val	missense	Exon 1 of 5	ENSP00000523319.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000840 AC: 10 AN: 1191180 Hom.: 0 Cov.: 33 AF XY: 0.0000120 AC XY: 7 AN XY: 582608

African (AFR) AF: 0.00 AC: 0 AN: 23622

American (AMR) AF: 0.00 AC: 0 AN: 13120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17406

East Asian (EAS) AF: 0.00 AC: 0 AN: 25846

South Asian (SAS) AF: 0.00 AC: 0 AN: 52132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3378

European-Non Finnish (NFE) AF: 0.0000102 AC: 10 AN: 980062

Other (OTH) AF: 0.00 AC: 0 AN: 47632

GnomAD4 genome Cov.: 34

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	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.087
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.25	N
REVEL	Benign	0.015
Sift	Benign	0.88	T
Sift4G	Benign	0.45	T
Polyphen		0.0030	B
Vest4		0.092
MutPred		0.16		Loss of disorder (P = 0.0624)
MVP		0.040
MPC		0.26
ClinPred		0.17	T
GERP RS		0.47
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.35
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

hg19: chr16-771300;