rs9323656

Variant names:

• chr14-77858227-T-C
• rs9323656
• NM_020421.4:c.220-849T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020421.4(ADCK1):​c.220-849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 152,128 control chromosomes in the GnomAD database, including 346 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.062 (346 hom., cov: 32)
• Consequence: ADCK1 NM_020421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCK1	NM_020421.4	c.220-849T>C		intron_variant	Intron 3 of 10	ENST00000238561.10	NP_065154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCK1	ENST00000238561.10	c.220-849T>C		intron_variant	Intron 3 of 10	1	NM_020421.4	ENSP00000238561.5

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9345 AN: 152010 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.0681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0615 AC: 9358 AN: 152128 Hom.: 346 Cov.: 32 AF XY: 0.0595 AC XY: 4424 AN XY: 74378

African (AFR) AF: 0.0346 AC: 1435 AN: 41524

American (AMR) AF: 0.0602 AC: 918 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3466

East Asian (EAS) AF: 0.00637 AC: 33 AN: 5182

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4812

European-Finnish (FIN) AF: 0.0682 AC: 723 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0813 AC: 5524 AN: 67978

Other (OTH) AF: 0.0669 AC: 141 AN: 2108

Alfa AF: 0.0778 Hom.: 772

Bravo AF: 0.0595

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.65
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9323656; hg19: chr14-78324570;