NM_020137.5:c.2107C>G

Variant names:

• chrX-48976318-G-C
• NM_020137.5:c.2107C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020137.5(GRIPAP1):​c.2107C>G​(p.Leu703Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GRIPAP1 NM_020137.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2269626).

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.2107C>G	p.Leu703Val	missense	Exon 23 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.2107C>G	p.Leu703Val	missense	Exon 23 of 26	ENSP00000365606.5	Q4V328-1
	GRIPAP1	ENST00000900849.1		c.2278C>G	p.Leu760Val	missense	Exon 25 of 28	ENSP00000570908.1
	GRIPAP1	ENST00000946827.1		c.2275C>G	p.Leu759Val	missense	Exon 25 of 28	ENSP00000616886.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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	0.35
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.29
MutPred		0.082		Loss of glycosylation at P698 (P = 0.2244)
MVP		0.79
ClinPred		0.89	D
GERP RS		3.5
Varity_R		0.21
gMVP		0.75
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-48832730;