X-48987841-C-T

Position:

• chrX-48987841-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020137.5(GRIPAP1):​c.985G>A​(p.Glu329Lys) variant causes a missense change. 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: 19)
• Consequence: GRIPAP1 NM_020137.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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

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=0.12001526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIPAP1	NM_020137.5	c.985G>A	p.Glu329Lys	missense_variant	13/26	ENST00000376423.8	NP_064522.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIPAP1	ENST00000376423.8	c.985G>A	p.Glu329Lys	missense_variant	13/26	1	NM_020137.5	ENSP00000365606	P3

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.985G>A (p.E329K) alteration is located in exon 13 (coding exon 13) of the GRIPAP1 gene. This alteration results from a G to A substitution at nucleotide position 985, causing the glutamic acid (E) at amino acid position 329 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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	.;L
MutationTaster	Benign	0.51	D;D;D;D
PrimateAI	Uncertain	0.60	T
REVEL	Benign	0.032
Sift4G	Benign	0.19	T;T
Polyphen		0.0070	.;B
Vest4		0.13
MutPred		0.30		.;Gain of ubiquitination at E329 (P = 0.0045);
MVP		0.31
ClinPred		0.76	D
GERP RS		3.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.15
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48844255;