16-721351-C-G

Variant names:

• chr16-721351-C-G
• rs979488558
• NM_023933.3:c.77C>G

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.77C>G​(p.Ala26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000843 in 1,186,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A26V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• 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=0.09392688).

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.77C>G	p.Ala26Gly	missense	Exon 1 of 5	NP_076422.1	Q9BQD7
	ANTKMT	NM_001271285.2		c.77C>G	p.Ala26Gly	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.77C>G	p.Ala26Gly	missense	Exon 1 of 5	ENSP00000454380.1	Q9BQD7
	ANTKMT	ENST00000853259.1		c.77C>G	p.Ala26Gly	missense	Exon 1 of 5	ENSP00000523318.1
	ANTKMT	ENST00000853260.1		c.77C>G	p.Ala26Gly	missense	Exon 1 of 5	ENSP00000523319.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.43e-7 AC: 1 AN: 1186666 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 579196

⚠️ 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: 23736

American (AMR) AF: 0.00 AC: 0 AN: 13390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17012

East Asian (EAS) AF: 0.00 AC: 0 AN: 25978

South Asian (SAS) AF: 0.00 AC: 0 AN: 50060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3280

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 978022

Other (OTH) AF: 0.00 AC: 0 AN: 47618

⚠️ 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.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.020
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.060
Sift	Benign	0.033	D
Sift4G	Uncertain	0.044	D
Polyphen		0.66	P
Vest4		0.15
MutPred		0.39		Gain of catalytic residue at A26 (P = 0.0116)
MVP		0.048
MPC		0.20
ClinPred		0.63	D
GERP RS		-4.3
PromoterAI		-0.045	Neutral
Varity_R		0.079
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs979488558; hg19: chr16-771351;