chr16-722354-G-A

Position:

• chr16-722354-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023933.3(ANTKMT):​c.505G>A​(p.Ala169Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

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]

ANTKMT (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31520915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANTKMT	NM_023933.3	c.505G>A	p.Ala169Thr	missense_variant	5/5	ENST00000569529.6	NP_076422.1
ANTKMT	NM_001271285.2	c.454G>A	p.Ala152Thr	missense_variant	4/4		NP_001258214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANTKMT	ENST00000569529.6	c.505G>A	p.Ala169Thr	missense_variant	5/5	1	NM_023933.3	ENSP00000454380.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.505G>A (p.A169T) alteration is located in exon 5 (coding exon 5) of the FAM173A gene. This alteration results from a G to A substitution at nucleotide position 505, causing the alanine (A) at amino acid position 169 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.0045	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	0.068
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.18
Sift	Benign	0.12	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.75	P;.
Vest4		0.36
MutPred		0.43		Gain of glycosylation at A169 (P = 0.0596);.;
MVP		0.28
MPC		0.37
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.77

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-772354;