rs10488907

Variant names:

• chr4-112390949-C-T
• rs10488907
• NM_025144.4:c.276+8397C>T

Variant summary

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

The NM_025144.4(ALPK1):​c.276+8397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,030 control chromosomes in the GnomAD database, including 3,266 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 0.18 (3266 hom., cov: 32)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

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.276+8397C>T		intron	N/A	NP_079420.3
	ALPK1	NM_001102406.2		c.276+8397C>T		intron	N/A	NP_001095876.1
	ALPK1	NM_001253884.2		c.42+13051C>T		intron	N/A	NP_001240813.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	ENST00000650871.1	MANE Select	c.276+8397C>T		intron	N/A	ENSP00000498374.1
	ALPK1	ENST00000177648.13	TSL:1	c.276+8397C>T		intron	N/A	ENSP00000177648.9
	ALPK1	ENST00000458497.6	TSL:5	c.276+8397C>T		intron	N/A	ENSP00000398048.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27401 AN: 151912 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 27395 AN: 152030 Hom.: 3266 Cov.: 32 AF XY: 0.180 AC XY: 13341 AN XY: 74304

African (AFR) AF: 0.0479 AC: 1986 AN: 41424

American (AMR) AF: 0.159 AC: 2432 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 962 AN: 3468

East Asian (EAS) AF: 0.0236 AC: 122 AN: 5178

South Asian (SAS) AF: 0.104 AC: 503 AN: 4816

European-Finnish (FIN) AF: 0.270 AC: 2848 AN: 10562

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17761 AN: 67968

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.217 Hom.: 8659

Bravo AF: 0.167

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.67
PhyloP100		-1.6
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: rs10488907; hg19: chr4-113312105;