Variant X-48978386-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020137.5(GRIPAP1):c.1980G>C(p.Gln660His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,207,147 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000028 ( 0 hom. 16 hem. )

Consequence

GRIPAP1
NM_020137.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07011351).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIPAP1	NM_020137.5 linkuse as main transcript	c.1980G>C	p.Gln660His	missense_variant	22/26	ENST00000376423.8	NP_064522.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIPAP1	ENST00000376423.8 linkuse as main transcript	c.1980G>C	p.Gln660His	missense_variant	22/26	1	NM_020137.5	ENSP00000365606	P3	Q4V328-1

Frequencies

GnomAD3 genomes

AF:

0.0000535

AC:

AN:

112048

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34182

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000940

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000452

AC:

AN:

176898

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

61776

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 SAS exome

AF:

0.000280

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000254

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1095045

Hom.:

Cov.:

AF XY:

0.0000444

AC XY:

AN XY:

360531

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000518

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000337

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000535

AC:

AN:

112102

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34246

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000940

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000291

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000494

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

Jun 07, 2023

The c.1980G>C (p.Q660H) alteration is located in exon 22 (coding exon 22) of the GRIPAP1 gene. This alteration results from a G to C substitution at nucleotide position 1980, causing the glutamine (Q) at amino acid position 660 to be replaced by a histidine (H). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

.;T;T

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.9

.;.;L

MutationTaster

Benign

0.63

D;D;D;D

PrimateAI

Uncertain

0.68

REVEL

Benign

0.11

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.51

.;.;P

Vest4

0.12

MutPred

0.11

.;.;Loss of helix (P = 0.0041);

MVP

0.82

ClinPred

0.41

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.41

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