14-77924563-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020421.4(ADCK1):​c.965C>T​(p.Thr322Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ADCK1
NM_020421.4 missense

Scores

6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.33646756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADCK1NM_020421.4 linkuse as main transcriptc.965C>T p.Thr322Met missense_variant 8/11 ENST00000238561.10 NP_065154.2 Q86TW2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADCK1ENST00000238561.10 linkuse as main transcriptc.965C>T p.Thr322Met missense_variant 8/111 NM_020421.4 ENSP00000238561.5 Q86TW2-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000439
AC:
11
AN:
250628
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135532
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461500
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727046
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000576
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 GeneticsSep 14, 2022The c.965C>T (p.T322M) alteration is located in exon 8 (coding exon 7) of the ADCK1 gene. This alteration results from a C to T substitution at nucleotide position 965, causing the threonine (T) at amino acid position 322 to be replaced by a methionine (M). 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
-0.24
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.34
T;T
MetaSVM
Uncertain
-0.22
T
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.21
Sift
Benign
0.061
T;T
Sift4G
Benign
0.085
T;T
Polyphen
1.0
D;.
Vest4
0.43
MVP
0.66
MPC
0.43
ClinPred
0.39
T
GERP RS
5.8
gMVP
0.49

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: rs759314185; hg19: chr14-78390906; COSMIC: COSV99452967; COSMIC: COSV99452967; API