4-89248511-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198281.3(GPRIN3):​c.1600G>A​(p.Asp534Asn) 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: 32)

Consequence

GPRIN3
NM_198281.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.342
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043018967).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPRIN3NM_198281.3 linkuse as main transcriptc.1600G>A p.Asp534Asn missense_variant 2/2 ENST00000609438.2 NP_938022.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPRIN3ENST00000609438.2 linkuse as main transcriptc.1600G>A p.Asp534Asn missense_variant 2/22 NM_198281.3 ENSP00000476603 P1
GPRIN3ENST00000333209.4 linkuse as main transcriptc.1600G>A p.Asp534Asn 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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 04, 2022The c.1600G>A (p.D534N) alteration is located in exon 2 (coding exon 1) of the GPRIN3 gene. This alteration results from a G to A substitution at nucleotide position 1600, causing the aspartic acid (D) at amino acid position 534 to be replaced by an asparagine (N). 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
0.082
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
6.4
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0023
T;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.47
.;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.043
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.55
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.56
.;N
REVEL
Benign
0.12
Sift
Benign
0.39
.;T
Sift4G
Benign
0.47
T;T
Polyphen
0.0020
B;B
Vest4
0.040
MutPred
0.10
Loss of ubiquitination at K538 (P = 0.0393);Loss of ubiquitination at K538 (P = 0.0393);
MVP
0.040
MPC
0.037
ClinPred
0.090
T
GERP RS
3.0
Varity_R
0.035
gMVP
0.062

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: chr4-90169662; API