Genetic Variant ALPK1:c.*256C>A (chr4-112441466-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025144.4(ALPK1):c.*256C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 389,324 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: 32)

Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

ALPK1
NM_025144.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0540

Publications

10 publications found

Variant links:

Genes affected

ALPK1 (HGNC:20917): (alpha kinase 1) This gene encodes an alpha kinase. Mice which were homozygous for disrupted copies of this gene exhibited coordination defects (PMID: 21208416). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ALPK1 Gene-Disease associations (from GenCC):

retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ALPK1 links:

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ACMG classification

Classification was made for transcript

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=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ALPK1	NM_025144.4 link	c.*256C>A	3_prime_UTR_variant	Exon 16 of 16	ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2 link	c.*256C>A	3_prime_UTR_variant	Exon 16 of 16		NP_001095876.1
ALPK1	NM_001253884.2 link	c.*256C>A	3_prime_UTR_variant	Exon 15 of 15		NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1 link	c.*256C>A		3_prime_UTR_variant	Exon 16 of 16		NM_025144.4	ENSP00000498374.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000257

AC:

AN:

389324

Hom.:

Cov.:

AF XY:

0.00000490

AC XY:

AN XY:

204094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11364

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12298

East Asian (EAS)

AF:

0.00

AC:

AN:

28316

South Asian (SAS)

AF:

0.00

AC:

AN:

36028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1724

European-Non Finnish (NFE)

AF:

0.00000425

AC:

AN:

235504

Other (OTH)

AF:

0.00

AC:

AN:

22976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

4084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.32

PhyloP100

-0.054

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over