chr8-144375777-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174922.5(ADCK5):​c.12+1670G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 442,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: ADCK5 NM_174922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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>A		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>A		intron	N/A	ENSP00000310547.6
	ADCK5	ENST00000529654.5	TSL:1	n.12+1670G>A		intron	N/A	ENSP00000431875.1
	ADCK5	ENST00000525136.1	TSL:3	n.225+140G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000226 AC: 1 AN: 442748 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 207730

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7908

American (AMR) AF: 0.00 AC: 0 AN: 500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2694

East Asian (EAS) AF: 0.00 AC: 0 AN: 1772

South Asian (SAS) AF: 0.00 AC: 0 AN: 8676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 916

European-Non Finnish (NFE) AF: 0.00000246 AC: 1 AN: 405744

Other (OTH) AF: 0.00 AC: 0 AN: 14384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-1.1

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;