16-721300-C-T

Position:

• chr16-721300-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 13/21 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026326388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTKMT	NM_023933.3	c.26C>T	p.Ala9Val	missense_variant	1/5	ENST00000569529.6
ANTKMT	NM_001271285.2	c.26C>T	p.Ala9Val	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTKMT	ENST00000569529.6	c.26C>T	p.Ala9Val	missense_variant	1/5	1	NM_023933.3	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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

Dec 05, 2022

The c.26C>T (p.A9V) alteration is located in exon 1 (coding exon 1) of the FAM173A gene. This alteration results from a C to T substitution at nucleotide position 26, causing the alanine (A) at amino acid position 9 to be replaced by a valine (V). 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	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.026	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.25	N;N;N
REVEL	Benign	0.015
Sift	Benign	0.88	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.092
MutPred		0.16		Loss of disorder (P = 0.0624);Loss of disorder (P = 0.0624);Loss of disorder (P = 0.0624);
MVP		0.040
MPC		0.26
ClinPred		0.17	T
GERP RS		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.35

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-771300;