3-141780606-A-C

Position:

• chr3-141780606-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139209.3(GRK7):​c.845A>C​(p.Asn282Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GRK7 NM_139209.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.870

Genes affected

GRK7 (HGNC:17031): (G protein-coupled receptor kinase 7) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. It is specifically expressed in the retina and the encoded protein has been shown to phosphorylate cone opsins and initiate their deactivation. [provided by RefSeq, Jul 2008]

ENSG00000285558 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14650154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK7	NM_139209.3	c.845A>C	p.Asn282Thr	missense_variant	4/6	ENST00000682958.1	NP_631948.1
GRK7	XM_047447449.1	c.845A>C	p.Asn282Thr	missense_variant	5/7		XP_047303405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK7	ENST00000682958.1	c.845A>C	p.Asn282Thr	missense_variant	4/6		NM_139209.3	ENSP00000508022.1
GRK7	ENST00000264952.2	c.845A>C	p.Asn282Thr	missense_variant	2/4	1		ENSP00000264952.2
ENSG00000285558	ENST00000648835.1	n.*186A>C		non_coding_transcript_exon_variant	2/3			ENSP00000498049.1
ENSG00000285558	ENST00000648835.1	n.*186A>C		3_prime_UTR_variant	2/3			ENSP00000498049.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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.845A>C (p.N282T) alteration is located in exon 2 (coding exon 2) of the GRK7 gene. This alteration results from a A to C substitution at nucleotide position 845, causing the asparagine (N) at amino acid position 282 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.063
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.068	T
Polyphen		0.26	B
Vest4		0.31
MutPred		0.45		Loss of catalytic residue at N282 (P = 0.012);
MVP		0.37
MPC		0.41
ClinPred		0.90	D
GERP RS		-4.1
Varity_R		0.46
gMVP		0.29

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: chr3-141499448;