chr5-176597515-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052899.3(GPRIN1):​c.2320G>A​(p.Glu774Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000941 in 1,476,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E774G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

GPRIN1
NM_052899.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.209

Publications

0 publications found
Variant links:
Genes affected
GPRIN1 (HGNC:24835): (G protein regulated inducer of neurite outgrowth 1) Predicted to enable phosphoprotein binding activity. Predicted to be involved in neuron projection development. Predicted to be located in growth cone. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.042346567).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPRIN1NM_052899.3 linkc.2320G>A p.Glu774Lys missense_variant Exon 2 of 2 ENST00000303991.5 NP_443131.2 Q7Z2K8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPRIN1ENST00000303991.5 linkc.2320G>A p.Glu774Lys missense_variant Exon 2 of 2 1 NM_052899.3 ENSP00000305839.4 Q7Z2K8-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000190
AC:
2
AN:
105136
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000485
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000944
AC:
125
AN:
1324664
Hom.:
0
Cov.:
30
AF XY:
0.0000740
AC XY:
48
AN XY:
648330
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28866
American (AMR)
AF:
0.0000352
AC:
1
AN:
28428
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22850
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33170
South Asian (SAS)
AF:
0.0000135
AC:
1
AN:
74246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32842
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4808
European-Non Finnish (NFE)
AF:
0.000114
AC:
119
AN:
1044708
Other (OTH)
AF:
0.0000731
AC:
4
AN:
54746
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
8
15
23
30
38
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74338
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41462
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000206
AC:
14
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000159
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000294
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 12, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.2320G>A (p.E774K) alteration is located in exon 2 (coding exon 1) of the GPRIN1 gene. This alteration results from a G to A substitution at nucleotide position 2320, causing the glutamic acid (E) at amino acid position 774 to be replaced by a lysine (K). 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
0.094
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
5.3
DANN
Benign
0.94
DEOGEN2
Benign
0.0041
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.46
N
PhyloP100
0.21
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.018
Sift
Benign
0.12
T
Sift4G
Benign
0.23
T
Polyphen
0.0010
B
Vest4
0.061
MutPred
0.23
Gain of ubiquitination at E774 (P = 0.0051);
MVP
0.068
ClinPred
0.030
T
GERP RS
-6.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.047
gMVP
0.13
Mutation Taster
=95/5
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

Publications

Other links and lift over

dbSNP: rs762024937; hg19: chr5-176024516; API