chr14-77887182-C-T

Variant names:

• chr14-77887182-C-T
• rs142511548
• NM_020421.4:c.515C>T

Variant summary

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

The NM_020421.4(ADCK1):​c.515C>T​(p.Thr172Met) variant causes a missense change. The variant allele was found at a frequency of 0.000183 in 1,610,126 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 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: ADCK1 NM_020421.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97
• Publications: 3 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=0.2385054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020421.4. 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.515C>T	p.Thr172Met	missense	Exon 5 of 11	NP_065154.2
	ADCK1	NM_001366487.2		c.515C>T	p.Thr172Met	missense	Exon 5 of 12	NP_001353416.1
	ADCK1	NM_001366485.2		c.515C>T	p.Thr172Met	missense	Exon 5 of 10	NP_001353414.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCK1	ENST00000238561.10	TSL:1 MANE Select	c.515C>T	p.Thr172Met	missense	Exon 5 of 11	ENSP00000238561.5	Q86TW2-2
	ADCK1	ENST00000951873.1		c.515C>T	p.Thr172Met	missense	Exon 5 of 13	ENSP00000621932.1
	ADCK1	ENST00000951875.1		c.515C>T	p.Thr172Met	missense	Exon 5 of 12	ENSP00000621934.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000134 AC: 33 AN: 247060 AF XY: 0.000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000560

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000187

Gnomad OTH exome AF: 0.000670

GnomAD4 exome AF: 0.000182 AC: 265 AN: 1457858 Hom.: 0 Cov.: 31 AF XY: 0.000200 AC XY: 145 AN XY: 725202

African (AFR) AF: 0.0000301 AC: 1 AN: 33210

American (AMR) AF: 0.000158 AC: 7 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.000280 AC: 11 AN: 39248

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.000205 AC: 228 AN: 1110064

Other (OTH) AF: 0.000232 AC: 14 AN: 60244

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74444

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.000261 AC: 4 AN: 15298

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

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

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

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.000219

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000659 AC: 8

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	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.80	T
PhyloP100		4.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.075
Sift	Benign	0.070	T
Sift4G	Benign	0.11	T
Polyphen		0.73	P
Vest4		0.67
MVP		0.57
MPC		0.20
ClinPred		0.054	T
GERP RS		5.9
gMVP		0.42
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142511548; hg19: chr14-78353525; COSMIC: COSV53079413;