Genetic Variant NM_020778.5:c.-91G>A (chr15-84817362-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020778.5(ALPK3):c.-91G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALPK3
NM_020778.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0680

Variant links:

Genes affected

ALPK3 (HGNC:17574): (alpha kinase 3) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in cardiac muscle cell development. Predicted to be active in nucleus. Implicated in hypertrophic cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ALPK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-84817362-G-A is Benign according to our data. Variant chr15-84817362-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3686298.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK3	NM_020778.5 link	c.-91G>A		5_prime_UTR_variant	Exon 1 of 14	ENST00000258888.6	NP_065829.4	Q96L96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6 link	c.-91G>A		5_prime_UTR_variant	Exon 1 of 14	1	NM_020778.5	ENSP00000258888.6		Q96L96

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1077010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509916

African (AFR)

AF:

0.00

AC:

AN:

22432

American (AMR)

AF:

0.00

AC:

AN:

8022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13852

East Asian (EAS)

AF:

0.00

AC:

AN:

25524

South Asian (SAS)

AF:

0.00

AC:

AN:

20556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2872

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

919348

Other (OTH)

AF:

0.00

AC:

AN:

43078

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

-0.068

PromoterAI

0.0010

Neutral

(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

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over