X-48981220-C-A

Variant names:

• chrX-48981220-C-A
• rs782625013
• NM_020137.5:c.1925G>T

Variant summary

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

The NM_020137.5(GRIPAP1):​c.1925G>T​(p.Arg642Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R642H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GRIPAP1 NM_020137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• Publications: 4 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.1925G>T	p.Arg642Leu	missense	Exon 21 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.1925G>T	p.Arg642Leu	missense	Exon 21 of 26	ENSP00000365606.5	Q4V328-1
	GRIPAP1	ENST00000900849.1		c.2000G>T	p.Arg667Leu	missense	Exon 22 of 28	ENSP00000570908.1
	GRIPAP1	ENST00000946827.1		c.2000G>T	p.Arg667Leu	missense	Exon 22 of 28	ENSP00000616886.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1089811 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 355917

African (AFR) AF: 0.00 AC: 0 AN: 26282

American (AMR) AF: 0.00 AC: 0 AN: 35021

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19319

East Asian (EAS) AF: 0.00 AC: 0 AN: 30160

South Asian (SAS) AF: 0.00 AC: 0 AN: 53338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3849

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 835782

Other (OTH) AF: 0.00 AC: 0 AN: 45832

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.1
PrimateAI	Pathogenic	0.79	T
REVEL	Benign	0.17
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.22		Loss of MoRF binding (P = 0.0406)
MVP		0.97
ClinPred		0.95	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.48
Mutation Taster		=72/28	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

dbSNP: rs782625013; hg19: chrX-48837632;