NM_020778.5:c.-91G>T

Variant names:

• chr15-84817362-G-T
• rs1963371012
• NM_020778.5:c.-91G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020778.5(ALPK3):​c.-91G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000928 in 1,077,010 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: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: ALPK3 NM_020778.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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]

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=-0.75).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.28e-7 AC: 1 AN: 1077010 Hom.: 0 Cov.: 51 AF XY: 0.00000196 AC XY: 1 AN XY: 509916

African (AFR) AF: 0.00 AC: 0 AN: 22432

American (AMR) AF: 0.00 AC: 0 AN: 8022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13852

East Asian (EAS) AF: 0.00 AC: 0 AN: 25524

South Asian (SAS) AF: 0.00 AC: 0 AN: 20556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2872

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919348

Other (OTH) AF: 0.00 AC: 0 AN: 43078

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		-0.068
PromoterAI		0.041	Neutral

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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Other links and lift over

dbSNP: rs1963371012; hg19: chr15-85360593;