Variant 14-77925839-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020421.4(ADCK1):c.1084A>G(p.Lys362Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000963 in 1,614,186 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

ADCK1
NM_020421.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Variant links:

Genes affected

ADCK1 (HGNC:19038): (aarF domain containing kinase 1) Predicted to enable ATP binding activity and protein serine/threonine kinase activity. Involved in negative regulation of mitochondrial fusion and positive regulation of cristae formation. Predicted to be located in extracellular region. Predicted to be active in mitochondrial inner membrane. Predicted to be integral component of mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADCK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.022262335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCK1	NM_020421.4 linkuse as main transcript	c.1084A>G	p.Lys362Glu	missense_variant	9/11	ENST00000238561.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCK1	ENST00000238561.10 linkuse as main transcript	c.1084A>G	p.Lys362Glu	missense_variant	9/11	1	NM_020421.4	P1	Q86TW2-2

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.000955

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000489

AC:

123

AN:

251492

Hom.:

AF XY:

0.000522

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000967

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.00101

AC:

1477

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

728

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000512

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.000533

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.00101

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 submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.1084A>G (p.K362E) alteration is located in exon 9 (coding exon 8) of the ADCK1 gene. This alteration results from a A to G substitution at nucleotide position 1084, causing the lysine (K) at amino acid position 362 to be replaced by a glutamic acid (E). 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

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.68

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.55

D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.12

Sift

Benign

0.13

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.018

B;.

Vest4

0.19

MVP

0.24

MPC

0.15

ClinPred

0.014

GERP RS

-1.9

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over