Genetic Variant ALPK1:c.*256C>G (chr4-112441466-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025144.4(ALPK1):c.*256C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 540,514 control chromosomes in the GnomAD database, including 120,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35184 hom., cov: 32)

Exomes 𝑓: 0.66 ( 85002 hom. )

Consequence

ALPK1
NM_025144.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0540

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 4-112441466-C-G is Benign according to our data. Variant chr4-112441466-C-G is described in ClinVar as [Benign]. Clinvar id is 1236964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALPK1	NM_025144.4 link	c.*256C>G	3_prime_UTR_variant	Exon 16 of 16	ENST00000650871.1	NP_079420.3	Q96QP1-1
ALPK1	NM_001102406.2 link	c.*256C>G	3_prime_UTR_variant	Exon 16 of 16		NP_001095876.1	Q96QP1-1
ALPK1	NM_001253884.2 link	c.*256C>G	3_prime_UTR_variant	Exon 15 of 15		NP_001240813.1	Q96QP1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1 link	c.*256C>G		3_prime_UTR_variant	Exon 16 of 16		NM_025144.4	ENSP00000498374.1		Q96QP1-1

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

103152

AN:

151990

Hom.:

35162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.723

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.677

GnomAD4 exome

AF:

0.660

AC:

256177

AN:

388406

Hom.:

85002

Cov.:

AF XY:

0.655

AC XY:

133371

AN XY:

203566

show subpopulations

Gnomad4 AFR exome

AF:

0.734

Gnomad4 AMR exome

AF:

0.598

Gnomad4 ASJ exome

AF:

0.713

Gnomad4 EAS exome

AF:

0.736

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.681

Gnomad4 NFE exome

AF:

0.658

Gnomad4 OTH exome

AF:

0.660

GnomAD4 genome

AF:

0.679

AC:

103227

AN:

152108

Hom.:

35184

Cov.:

AF XY:

0.678

AC XY:

50388

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.735

Gnomad4 AMR

AF:

0.618

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.723

Gnomad4 SAS

AF:

0.576

Gnomad4 FIN

AF:

0.691

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.676

Alfa

AF:

0.675

Hom.:

4084

Bravo

AF:

0.677

Asia WGS

AF:

0.587

AC:

2045

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 14, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23569188) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.3

DANN

Benign

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over