4-89248007-C-G

Position:

• chr4-89248007-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_198281.3(GPRIN3):​c.2104G>C​(p.Ala702Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPRIN3 NM_198281.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.45

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058576524).
• BP6: Variant 4-89248007-C-G is Benign according to our data. Variant chr4-89248007-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2306745.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRIN3	NM_198281.3	c.2104G>C	p.Ala702Pro	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.2104G>C	p.Ala702Pro	missense_variant	2/2	2	NM_198281.3	ENSP00000476603	P1
GPRIN3	ENST00000333209.4	c.2104G>C	p.Ala702Pro	missense_variant	1/1			ENSP00000328672	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.025
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.19
DEOGEN2	Benign	0.0067	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	N;N
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	3.6	.;N
REVEL	Benign	0.12
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.11
MutPred		0.44		Gain of catalytic residue at A702 (P = 0.0469);Gain of catalytic residue at A702 (P = 0.0469);
MVP		0.24
MPC		0.045
ClinPred		0.11	T
GERP RS		4.3
Varity_R		0.097
gMVP		0.19

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: chr4-90169158;