4-89247808-C-G

Position:

• chr4-89247808-C-G

Variant summary

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

The NM_198281.3(GPRIN3):​c.2303G>C​(p.Arg768Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPRIN3 NM_198281.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

Genes affected

GPRIN3 (HGNC:27733): (GPRIN family member 3) Predicted to be involved in neuron projection development. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
GPRIN3	NM_198281.3	c.2303G>C	p.Arg768Pro	missense_variant	2/2	ENST00000609438.2	NP_938022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRIN3	ENST00000609438.2	c.2303G>C	p.Arg768Pro	missense_variant	2/2	2	NM_198281.3	ENSP00000476603	P1
GPRIN3	ENST00000333209.4	c.2303G>C	p.Arg768Pro	missense_variant	1/1			ENSP00000328672	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Jan 17, 2024

The c.2303G>C (p.R768P) alteration is located in exon 2 (coding exon 1) of the GPRIN3 gene. This alteration results from a G to C substitution at nucleotide position 2303, causing the arginine (R) at amino acid position 768 to be replaced by a proline (P). 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	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.90	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.3	.;D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;D
Vest4		0.76
MutPred		0.38		Loss of MoRF binding (P = 0.0182);Loss of MoRF binding (P = 0.0182);
MVP		0.055
MPC		0.32
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.64
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs145667508; hg19: chr4-90168959;