NM_005160.4:c.161C>T

Variant names:

• chr22-25604424-C-T
• NM_005160.4:c.161C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005160.4(GRK3):​c.161C>T​(p.Thr54Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,398 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GRK3 NM_005160.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.89

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3	NM_005160.4	c.161C>T	p.Thr54Ile	missense_variant	Exon 2 of 21	ENST00000324198.11	NP_005151.2
GRK3	XM_047441166.1	c.56C>T	p.Thr19Ile	missense_variant	Exon 2 of 21		XP_047297122.1
GRK3	XM_047441167.1	c.161C>T	p.Thr54Ile	missense_variant	Exon 2 of 14		XP_047297123.1
GRK3	NM_001362778.2	c.-105C>T		5_prime_UTR_variant	Exon 2 of 20		NP_001349707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK3	ENST00000324198.11	c.161C>T	p.Thr54Ile	missense_variant	Exon 2 of 21	1	NM_005160.4	ENSP00000317578.4
GRK3	ENST00000455558.2	n.95C>T		non_coding_transcript_exon_variant	Exon 2 of 9	5		ENSP00000393688.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459398 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726024

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: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0085	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.20
Sift	Uncertain	0.013	D;.
Sift4G	Benign	0.13	T;T
Polyphen		0.93	P;.
Vest4		0.86
MutPred		0.58		Gain of methylation at K57 (P = 0.103);Gain of methylation at K57 (P = 0.103);
MVP		0.043
MPC		0.94
ClinPred		0.97	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-26000391;