rs772067720

Variant names:

• chr4-98404549-A-G
• rs772067720
• NM_001100427.2:c.710A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001100427.2(RAP1GDS1):​c.710A>G​(p.Glu237Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,607,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: RAP1GDS1 NM_001100427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25811684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100427.2. 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
	RAP1GDS1	NM_001100427.2	MANE Select	c.710A>G	p.Glu237Gly	missense	Exon 7 of 15	NP_001093897.1	P52306-1
	RAP1GDS1	NM_001100426.2		c.713A>G	p.Glu238Gly	missense	Exon 7 of 15	NP_001093896.1	P52306-5
	RAP1GDS1	NM_021159.5		c.713A>G	p.Glu238Gly	missense	Exon 7 of 15	NP_066982.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GDS1	ENST00000408927.8	TSL:2 MANE Select	c.710A>G	p.Glu237Gly	missense	Exon 7 of 15	ENSP00000386153.4	P52306-1
	RAP1GDS1	ENST00000339360.9	TSL:1	c.713A>G	p.Glu238Gly	missense	Exon 7 of 15	ENSP00000340454.5	P52306-5
	RAP1GDS1	ENST00000453712.6	TSL:1	c.713A>G	p.Glu238Gly	missense	Exon 7 of 15	ENSP00000407157.2	P52306-4

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 5 AN: 243098 AF XY: 0.00

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1455408 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 723784

African (AFR) AF: 0.0000605 AC: 2 AN: 33084

American (AMR) AF: 0.0000687 AC: 3 AN: 43648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39268

South Asian (SAS) AF: 0.00 AC: 0 AN: 84710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109482

Other (OTH) AF: 0.0000333 AC: 2 AN: 60138

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74338

African (AFR) AF: 0.000289 AC: 12 AN: 41460

American (AMR) AF: 0.000262 AC: 4 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.000144

ExAC AF: 0.00000828 AC: 1

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	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.76	N
PhyloP100		8.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.63	N
REVEL	Uncertain	0.31
Sift	Benign	0.73	T
Sift4G	Benign	0.74	T
Polyphen		0.0020	B
Vest4		0.81
MVP		0.50
MPC		0.20
ClinPred		0.21	T
GERP RS		5.7
Varity_R		0.42
gMVP		0.57
Mutation Taster		=16/84	disease causing

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: rs772067720; hg19: chr4-99325700;