14-77822517-A-T

Variant names:

• chr14-77822517-A-T
• rs369693118
• NM_020421.4:c.218A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001366490.2(ADCK1):​c.-279A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000515 in 1,612,892 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: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: ADCK1 NM_001366490.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.3755
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17704296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366490.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCK1	NM_020421.4	MANE Select	c.218A>T	p.Lys73Met	missense splice_region	Exon 3 of 11	NP_065154.2
	ADCK1	NM_001366490.2		c.-279A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	NP_001353419.1
	ADCK1	NM_001366487.2		c.218A>T	p.Lys73Met	missense splice_region	Exon 3 of 12	NP_001353416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCK1	ENST00000238561.10	TSL:1 MANE Select	c.218A>T	p.Lys73Met	missense splice_region	Exon 3 of 11	ENSP00000238561.5	Q86TW2-2
	ADCK1	ENST00000951873.1		c.218A>T	p.Lys73Met	missense splice_region	Exon 3 of 13	ENSP00000621932.1
	ADCK1	ENST00000951875.1		c.218A>T	p.Lys73Met	missense splice_region	Exon 3 of 12	ENSP00000621934.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251400 AF XY: 0.0000662

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1460602 Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25 AN XY: 726718

African (AFR) AF: 0.000717 AC: 24 AN: 33450

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1110832

Other (OTH) AF: 0.000149 AC: 9 AN: 60358

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74454

African (AFR) AF: 0.000481 AC: 20 AN: 41574

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000227

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.9
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.047	D
Polyphen		0.66	P
Vest4		0.43
MVP		0.93
MPC		0.35
ClinPred		0.089	T
GERP RS		4.9
gMVP		0.51
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.38
dbscSNV1_RF	Benign	0.52
Splicevardb		1.0
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

Other links and lift over

dbSNP: rs369693118; hg19: chr14-78288860;