chr4-112441466-C-A

Variant names:

• chr4-112441466-C-A
• rs231253
• NM_025144.4:c.*256C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 10 publications found

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

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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025144.4. 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
	ALPK1	NM_025144.4	MANE Select	c.*256C>A		3_prime_UTR	Exon 16 of 16	NP_079420.3
	ALPK1	NM_001102406.2		c.*256C>A		3_prime_UTR	Exon 16 of 16	NP_001095876.1
	ALPK1	NM_001253884.2		c.*256C>A		3_prime_UTR	Exon 15 of 15	NP_001240813.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	ENST00000650871.1	MANE Select	c.*256C>A		3_prime_UTR	Exon 16 of 16	ENSP00000498374.1
	ALPK1	ENST00000177648.13	TSL:1	c.*256C>A		3_prime_UTR	Exon 16 of 16	ENSP00000177648.9
	ALPK1	ENST00000504745.1	TSL:2	n.4479C>A		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000257 AC: 1 AN: 389324 Hom.: 0 Cov.: 2 AF XY: 0.00000490 AC XY: 1 AN XY: 204094

African (AFR) AF: 0.00 AC: 0 AN: 11364

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12298

East Asian (EAS) AF: 0.00 AC: 0 AN: 28316

South Asian (SAS) AF: 0.00 AC: 0 AN: 36028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1724

European-Non Finnish (NFE) AF: 0.00000425 AC: 1 AN: 235504

Other (OTH) AF: 0.00 AC: 0 AN: 22976

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
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

Other links and lift over

dbSNP: rs231253; hg19: chr4-113362622;