X-48981676-G-C

Position:

• chrX-48981676-G-C

Variant summary

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

The NM_020137.5(GRIPAP1):​c.1693C>G​(p.Leu565Val) 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. 12/18 in silico tools predict a benign outcome for this variant. 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: 1.69

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=0.07151362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIPAP1	NM_020137.5	c.1693C>G	p.Leu565Val	missense_variant	19/26	ENST00000376423.8	NP_064522.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIPAP1	ENST00000376423.8	c.1693C>G	p.Leu565Val	missense_variant	19/26	1	NM_020137.5	ENSP00000365606	P3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

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

Mar 25, 2022

The c.1693C>G (p.L565V) alteration is located in exon 19 (coding exon 19) of the GRIPAP1 gene. This alteration results from a C to G substitution at nucleotide position 1693, causing the leucine (L) at amino acid position 565 to be replaced by a valine (V). 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	0.077
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.010	.;T;T
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.85	T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;.;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.41	T
REVEL	Benign	0.036
Sift4G	Benign	0.22	T;T;T
Polyphen		0.0040	.;.;B
Vest4		0.085
MutPred		0.20		.;.;Loss of glycosylation at K561 (P = 0.2972);
MVP		0.39
ClinPred		0.085	T
GERP RS		3.7
Varity_R		0.097
gMVP		0.073

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48838088;