8-144375777-G-C

Variant names:

• chr8-144375777-G-C
• rs4380978
• NM_174922.5:c.12+1670G>C

Variant summary

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

The NM_174922.5(ADCK5):​c.12+1670G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 592,950 control chromosomes in the GnomAD database, including 56,529 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 0.42 (14189 hom., cov: 33)
  • Exomes 𝑓: 0.43 (42340 hom.)
• Consequence: ADCK5 NM_174922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 18 publications found

Genes affected

ADCK5 (HGNC:21738): (aarF domain containing kinase 5) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be integral component of 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174922.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCK5	NM_174922.5	MANE Select	c.12+1670G>C		intron	N/A	NP_777582.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCK5	ENST00000308860.11	TSL:1 MANE Select	c.12+1670G>C		intron	N/A	ENSP00000310547.6
	ADCK5	ENST00000529654.5	TSL:1	n.12+1670G>C		intron	N/A	ENSP00000431875.1
	ADCK5	ENST00000525136.1	TSL:3	n.225+140G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64437 AN: 151990 Hom.: 14177 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.433 AC: 191006 AN: 440842 Hom.: 42340 AF XY: 0.434 AC XY: 89778 AN XY: 206800

African (AFR) AF: 0.329 AC: 2598 AN: 7888

American (AMR) AF: 0.520 AC: 260 AN: 500

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 917 AN: 2684

East Asian (EAS) AF: 0.656 AC: 1158 AN: 1764

South Asian (SAS) AF: 0.583 AC: 5042 AN: 8644

European-Finnish (FIN) AF: 0.467 AC: 71 AN: 152

Middle Eastern (MID) AF: 0.360 AC: 328 AN: 912

European-Non Finnish (NFE) AF: 0.432 AC: 174455 AN: 403974

Other (OTH) AF: 0.431 AC: 6177 AN: 14324

GnomAD4 genome AF: 0.424 AC: 64475 AN: 152108 Hom.: 14189 Cov.: 33 AF XY: 0.430 AC XY: 31943 AN XY: 74364

African (AFR) AF: 0.338 AC: 14015 AN: 41486

American (AMR) AF: 0.494 AC: 7542 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3466

East Asian (EAS) AF: 0.641 AC: 3316 AN: 5170

South Asian (SAS) AF: 0.590 AC: 2849 AN: 4830

European-Finnish (FIN) AF: 0.487 AC: 5155 AN: 10580

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.426 AC: 28984 AN: 67980

Other (OTH) AF: 0.411 AC: 869 AN: 2114

Alfa AF: 0.274 Hom.: 674

Bravo AF: 0.422

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.88
DANN	Benign	0.30
PhyloP100		-1.1
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: rs4380978; hg19: chr8-145599466;