10-119423182-C-T

Variant names:

• chr10-119423182-C-T
• rs55980792
• NM_005308.3:c.356C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005308.3(GRK5):​c.356C>T​(p.Ala119Val) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,613,126 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (5 hom., cov: 33)
  • Exomes 𝑓: 0.011 (113 hom.)
• Consequence: GRK5 NM_005308.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.67
• Publications: 10 publications found

Genes affected

GRK5 (HGNC:4544): (G protein-coupled receptor kinase 5) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006025046).
• BP6: Variant 10-119423182-C-T is Benign according to our data. Variant chr10-119423182-C-T is described in ClinVar as Benign. ClinVar VariationId is 773238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1057 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005308.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	NM_005308.3	MANE Select	c.356C>T	p.Ala119Val	missense	Exon 5 of 16	NP_005299.1	P34947

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	ENST00000392870.3	TSL:1 MANE Select	c.356C>T	p.Ala119Val	missense	Exon 5 of 16	ENSP00000376609.2	P34947
	GRK5	ENST00000857196.1		c.356C>T	p.Ala119Val	missense	Exon 5 of 16	ENSP00000527255.1
	GRK5	ENST00000857197.1		c.356C>T	p.Ala119Val	missense	Exon 5 of 16	ENSP00000527256.1

Frequencies

GnomAD3 genomes AF: 0.00694 AC: 1057 AN: 152224 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00673 AC: 1693 AN: 251430 AF XY: 0.00677

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00342

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.0108 AC: 15774 AN: 1460784 Hom.: 113 Cov.: 30 AF XY: 0.0106 AC XY: 7700 AN XY: 726754

African (AFR) AF: 0.00182 AC: 61 AN: 33462

American (AMR) AF: 0.00340 AC: 152 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 44 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86246

European-Finnish (FIN) AF: 0.00401 AC: 214 AN: 53396

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0133 AC: 14738 AN: 1111008

Other (OTH) AF: 0.00901 AC: 544 AN: 60360

GnomAD4 genome AF: 0.00694 AC: 1057 AN: 152342 Hom.: 5 Cov.: 33 AF XY: 0.00647 AC XY: 482 AN XY: 74502

African (AFR) AF: 0.00267 AC: 111 AN: 41578

American (AMR) AF: 0.00431 AC: 66 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 829 AN: 68028

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.0103 Hom.: 15

Bravo AF: 0.00706

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0126 AC: 108

ExAC AF: 0.00696 AC: 845

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00960

EpiControl AF: 0.0101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		3.7
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.054
Sift	Uncertain	0.025	D
Sift4G	Benign	0.22	T
Polyphen		0.0010	B
Vest4		0.17
MVP		0.33
MPC		0.93
ClinPred		0.016	T
GERP RS		3.8
Varity_R		0.21
gMVP		0.54
Mutation Taster		=96/4	polymorphism

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: rs55980792; hg19: chr10-121182694;