22-25727521-C-T

Variant names:

• chr22-25727521-C-T
• rs133839
• NM_005160.4:c.*5071C>T

Variant summary

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

The NM_005160.4(GRK3):​c.*5071C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 152,358 control chromosomes in the GnomAD database, including 72,993 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 0.98 (72993 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: GRK3 NM_005160.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 3 publications found

Genes affected

GRK3 (HGNC:290): (G protein-coupled receptor kinase 3) The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3	NM_005160.4	c.*5071C>T		3_prime_UTR_variant	Exon 21 of 21	ENST00000324198.11	NP_005151.2
GRK3	NM_001362778.2	c.*5071C>T		3_prime_UTR_variant	Exon 20 of 20		NP_001349707.1
GRK3	XM_047441166.1	c.*5071C>T		3_prime_UTR_variant	Exon 21 of 21		XP_047297122.1
GRK3	XM_011529975.3	c.*5071C>T		3_prime_UTR_variant	Exon 18 of 18		XP_011528277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK3	ENST00000324198.11	c.*5071C>T		3_prime_UTR_variant	Exon 21 of 21	1	NM_005160.4	ENSP00000317578.4

Frequencies

GnomAD3 genomes AF: 0.979 AC: 149000 AN: 152240 Hom.: 72932 Cov.: 34

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.963

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.979 AC: 149120 AN: 152358 Hom.: 72993 Cov.: 34 AF XY: 0.980 AC XY: 73020 AN XY: 74506

African (AFR) AF: 0.995 AC: 41366 AN: 41570

American (AMR) AF: 0.969 AC: 14828 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3312 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5189 AN: 5192

South Asian (SAS) AF: 0.993 AC: 4796 AN: 4828

European-Finnish (FIN) AF: 0.992 AC: 10549 AN: 10630

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65904 AN: 68040

Other (OTH) AF: 0.963 AC: 2036 AN: 2114

Alfa AF: 0.969 Hom.: 83611

Bravo AF: 0.977

Asia WGS AF: 0.994 AC: 3454 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.48
PhyloP100		-0.27
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: rs133839; hg19: chr22-26123488;