Genetic Variant ADCK5:c.12+1670G>C (chr8-144375777-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

18 publications found

Variant links:

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]

ADCK5 links:

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ACMG classification

Classification was made for transcript

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

Sel.	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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCK5	ENST00000308860.11	TSL:1 MANE Select	c.12+1670G>C	intron	N/A	ENSP00000310547.6	Q3MIX3
ADCK5	ENST00000529654.5	TSL:1	n.12+1670G>C	intron	N/A	ENSP00000431875.1	E9PJ20
ADCK5	ENST00000886485.1		c.12+1670G>C	intron	N/A	ENSP00000556544.1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64437

AN:

151990

Hom.:

14177

Cov.:

show subpopulations

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

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5129

10259

15388

20518

25647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7204

14408

21612

28816

36020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.424

AC:

64475

AN:

152108

Hom.:

14189

Cov.:

AF XY:

0.430

AC XY:

31943

AN XY:

74364

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.426

AC:

28984

AN:

67980

Other (OTH)

AF:

0.411

AC:

869

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1891

3783

5674

7566

9457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.30

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over