Variant X-48981652-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020137.5(GRIPAP1):c.1717G>A(p.Glu573Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,208,206 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000010 ( 0 hom. 0 hem. )

Consequence

GRIPAP1
NM_020137.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

GRIPAP1 (HGNC:18706): (GRIP1 associated protein 1) This gene encodes a guanine nucleotide exchange factor for the Ras family of small G proteins (RasGEF). The encoded protein interacts in a complex with glutamate receptor interacting protein 1 (GRIP1) and plays a role in the regulation of AMPA receptor function. [provided by RefSeq, Aug 2013]

GRIPAP1 links:

GRIPAP1 (HGNC:):

GRIPAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07113078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIPAP1	NM_020137.5 linkuse as main transcript	c.1717G>A	p.Glu573Lys	missense_variant	19/26	ENST00000376423.8	NP_064522.4	Q4V328-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIPAP1	ENST00000376423.8 linkuse as main transcript	c.1717G>A	p.Glu573Lys	missense_variant	19/26	1	NM_020137.5	ENSP00000365606.5		Q4V328-1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112379

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34541

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

182859

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67337

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000526

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1095827

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361231

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.0000495

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112379

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34541

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000564

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Jul 22, 2024

The c.1717G>A (p.E573K) alteration is located in exon 19 (coding exon 19) of the GRIPAP1 gene. This alteration results from a G to A substitution at nucleotide position 1717, causing the glutamic acid (E) at amino acid position 573 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

0.060

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

.;T;T

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

.;.;N

REVEL

Benign

0.079

Sift

Benign

0.071

.;.;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.014

.;.;B

Vest4

0.038

MutPred

0.23

.;.;Gain of ubiquitination at E573 (P = 0.0029);

MVP

0.068

ClinPred

0.046

GERP RS

3.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.063

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over