X-48981432-T-C

Variant names:

• chrX-48981432-T-C
• NM_020137.5:c.1814A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020137.5(GRIPAP1):​c.1814A>G​(p.Lys605Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: GRIPAP1 NM_020137.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020137.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIPAP1	NM_020137.5	MANE Select	c.1814A>G	p.Lys605Arg	missense	Exon 20 of 26	NP_064522.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIPAP1	ENST00000376423.8	TSL:1 MANE Select	c.1814A>G	p.Lys605Arg	missense	Exon 20 of 26	ENSP00000365606.5	Q4V328-1
	GRIPAP1	ENST00000900849.1		c.1889A>G	p.Lys630Arg	missense	Exon 21 of 28	ENSP00000570908.1
	GRIPAP1	ENST00000946827.1		c.1889A>G	p.Lys630Arg	missense	Exon 21 of 28	ENSP00000616886.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.1
PrimateAI	Uncertain	0.69	T
REVEL	Benign	0.22
Sift4G	Benign	0.28	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.12		Loss of ubiquitination at K605 (P = 0.0071)
MVP		0.90
ClinPred		0.98	D
GERP RS		4.8
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.8
Varity_R		0.14
gMVP		0.34
Mutation Taster		=92/8	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

Other links and lift over

hg19: chrX-48837844; COSMIC: COSV64551083; COSMIC: COSV64551083;