chr14-77907803-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000238561.10(ADCK1):​c.742G>T​(p.Val248Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ADCK1
ENST00000238561.10 missense, splice_region

Scores

3
11
2
Splicing: ADA: 0.9258
1
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADCK1NM_020421.4 linkuse as main transcriptc.742G>T p.Val248Phe missense_variant, splice_region_variant 7/11 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.742G>T p.Val248Phe missense_variant, splice_region_variant 7/111 NM_020421.4 ENSP00000238561.5 Q86TW2-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

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 20, 2024The c.742G>T (p.V248F) alteration is located in exon 7 (coding exon 6) of the ADCK1 gene. This alteration results from a G to T substitution at nucleotide position 742, causing the valine (V) at amino acid position 248 to be replaced by a phenylalanine (F). 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
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
28
DANN
Uncertain
0.99
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Benign
-0.32
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.8
D;D
REVEL
Uncertain
0.50
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
0.99
D;.
Vest4
0.91
MutPred
0.77
Gain of ubiquitination at K247 (P = 0.0728);.;
MVP
0.70
MPC
0.50
ClinPred
0.99
D
GERP RS
3.0
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.93
dbscSNV1_RF
Pathogenic
0.75
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-78374146; API