NM_001100427.2:c.241A>G

Variant names:

• chr4-98352481-A-G
• rs764525858
• NM_001100427.2:c.241A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001100427.2(RAP1GDS1):​c.241A>G​(p.Met81Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 0.000021 (1 hom.)
• Consequence: RAP1GDS1 NM_001100427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.82
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32724088).

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.241A>G	p.Met81Val	missense	Exon 4 of 15	NP_001093897.1	P52306-1
	RAP1GDS1	NM_001100426.2		c.244A>G	p.Met82Val	missense	Exon 4 of 15	NP_001093896.1	P52306-5
	RAP1GDS1	NM_021159.5		c.244A>G	p.Met82Val	missense	Exon 4 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.241A>G	p.Met81Val	missense	Exon 4 of 15	ENSP00000386153.4	P52306-1
	RAP1GDS1	ENST00000339360.9	TSL:1	c.244A>G	p.Met82Val	missense	Exon 4 of 15	ENSP00000340454.5	P52306-5
	RAP1GDS1	ENST00000453712.6	TSL:1	c.244A>G	p.Met82Val	missense	Exon 4 of 15	ENSP00000407157.2	P52306-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 249122 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461134 Hom.: 1 Cov.: 30 AF XY: 0.0000330 AC XY: 24 AN XY: 726864

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111530

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.29
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.079
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PhyloP100		8.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.15
Sift	Benign	0.47	T
Sift4G	Benign	0.46	T
Polyphen		0.019	B
Vest4		0.80
MutPred		0.53		Gain of ubiquitination at K77 (P = 0.078)
MVP		0.48
MPC		0.18
ClinPred		0.24	T
GERP RS		5.8
Varity_R		0.34
gMVP		0.55
Mutation Taster		=69/31	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: rs764525858; hg19: chr4-99273632;