16-721919-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023933.3(ANTKMT):ā€‹c.386A>Gā€‹(p.Tyr129Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,572,664 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00013 ( 0 hom., cov: 35)
Exomes š‘“: 0.00011 ( 0 hom. )

Consequence

ANTKMT
NM_023933.3 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANTKMTNM_023933.3 linkuse as main transcriptc.386A>G p.Tyr129Cys missense_variant 3/5 ENST00000569529.6
ANTKMTNM_001271285.2 linkuse as main transcriptc.386A>G p.Tyr129Cys missense_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANTKMTENST00000569529.6 linkuse as main transcriptc.386A>G p.Tyr129Cys missense_variant 3/51 NM_023933.3 P1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152176
Hom.:
0
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000105
AC:
19
AN:
181632
Hom.:
0
AF XY:
0.0000995
AC XY:
10
AN XY:
100496
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000359
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000690
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000209
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000113
AC:
160
AN:
1420370
Hom.:
0
Cov.:
61
AF XY:
0.000116
AC XY:
82
AN XY:
704360
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000255
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000258
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000139
Gnomad4 OTH exome
AF:
0.0000843
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152294
Hom.:
0
Cov.:
35
AF XY:
0.000107
AC XY:
8
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000984
Hom.:
0
Bravo
AF:
0.000132
ExAC
AF:
0.0000603
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 18, 2022The c.386A>G (p.Y129C) alteration is located in exon 3 (coding exon 3) of the FAM173A gene. This alteration results from a A to G substitution at nucleotide position 386, causing the tyrosine (Y) at amino acid position 129 to be replaced by a cysteine (C). 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
Pathogenic
0.69
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
T;T;T
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.055
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Benign
0.059
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-5.9
D;D;D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.66
MutPred
0.62
Loss of catalytic residue at Y129 (P = 0.092);Loss of catalytic residue at Y129 (P = 0.092);Loss of catalytic residue at Y129 (P = 0.092);
MVP
0.32
MPC
0.50
ClinPred
0.52
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.71
gMVP
0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755241513; hg19: chr16-771919; API