20-44618291-A-G

Position:

• chr20-44618291-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001281445.2(PKIG):​c.158A>G​(p.Gln53Arg) variant causes a missense change. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKIG NM_001281445.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

Genes affected

PKIG (HGNC:9019): (cAMP-dependent protein kinase inhibitor gamma) This gene encodes a member of the protein kinase inhibitor family. Studies of a similar protein in mice suggest that this protein acts as a potent competitive cAMP-dependent protein kinase inhibitor, and is a predominant form of inhibitor in various tissues. The encoded protein may be involved in osteogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ADA (HGNC:186): (adenosine deaminase) This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia. [provided by RefSeq, Sep 2019]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40886614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKIG	NM_001281445.2	c.158A>G	p.Gln53Arg	missense_variant	4/4	ENST00000372886.6	NP_001268374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKIG	ENST00000372886.6	c.158A>G	p.Gln53Arg	missense_variant	4/4	2	NM_001281445.2	ENSP00000361977.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1456500 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.158A>G (p.Q53R) alteration is located in exon 6 (coding exon 2) of the PKIG gene. This alteration results from a A to G substitution at nucleotide position 158, causing the glutamine (Q) at amino acid position 53 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T;T;T;T;T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.61	.;.;.;.;.;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.41	T;T;T;T;T;T
MetaSVM	Uncertain	-0.17	T
MutationTaster	Benign	0.52	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.017	D;D;D;D;D;D
Sift4G	Uncertain	0.059	T;T;T;T;T;T
Polyphen		0.98	D;D;D;D;D;D
Vest4		0.31
MutPred		0.36		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.62
MPC		1.0
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43246932;