4-98416771-G-A

Variant names:

• chr4-98416771-G-A
• NM_001100427.2:c.790G>A

Variant summary

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

The NM_001100427.2(RAP1GDS1):​c.790G>A​(p.Ala264Thr) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAP1GDS1 NM_001100427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

Genes affected

RAP1GDS1 (HGNC:9859): (Rap1 GTPase-GDP dissociation stimulator 1) The smg GDP dissociation stimulator (smgGDS) protein is a stimulatory GDP/GTP exchange protein with GTPase activity (Riess et al., 1993 [PubMed 8262526]).[supplied by OMIM, Feb 2010]

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=0.2273646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1GDS1	NM_001100427.2	c.790G>A	p.Ala264Thr	missense_variant	Exon 8 of 15	ENST00000408927.8	NP_001093897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1GDS1	ENST00000408927.8	c.790G>A	p.Ala264Thr	missense_variant	Exon 8 of 15	2	NM_001100427.2	ENSP00000386153.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.793G>A (p.A265T) alteration is located in exon 8 (coding exon 8) of the RAP1GDS1 gene. This alteration results from a G to A substitution at nucleotide position 793, causing the alanine (A) at amino acid position 265 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.00027	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	.;.;T;.;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	.;.;M;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.024	D;D;D;D;D;D
Sift4G	Benign	0.064	T;T;T;T;T;T
Polyphen		0.23, 1.0	.;.;B;.;D;.
Vest4		0.42
MutPred		0.44		.;.;Loss of helix (P = 0.1299);.;.;.;
MVP		0.32
MPC		0.19
ClinPred		0.92	D
GERP RS		3.6
Varity_R		0.59
gMVP		0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-99337922;