rs371502735

Variant names:

• chrX-132214254-G-C
• rs371502735
• NM_001271186.2:c.466C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-132214254-G-C
• chrX-132214254-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001271186.2(RAP2C):​c.466C>G​(p.Leu156Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,210,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000017 (0 hom. 5 hem.)
• Consequence: RAP2C NM_001271186.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63
• Publications: 1 publications found

Genes affected

RAP2C (HGNC:21165): (RAP2C, member of RAS oncogene family) The protein encoded by this gene is a member of the Ras-related protein subfamily of the Ras GTPase superfamily. Members of this family are small GTPases that act as molecular switches to regulate cellular proliferation, differentiation, and apoptosis. This protein has been reported to activate in vitro transcriptional activity of the serum response element. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

RAP2C-AS1 (HGNC:40957): (RAP2C antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20380092).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271186.2. 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
	RAP2C	NM_001271186.2	MANE Select	c.466C>G	p.Leu156Val	missense	Exon 5 of 6	NP_001258115.1	Q9Y3L5
	RAP2C	NM_021183.5		c.466C>G	p.Leu156Val	missense	Exon 3 of 4	NP_067006.3
	RAP2C	NM_001271187.2		c.268C>G	p.Leu90Val	missense	Exon 5 of 6	NP_001258116.1	A0A087X2C3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP2C	ENST00000370874.2	TSL:2 MANE Select	c.466C>G	p.Leu156Val	missense	Exon 5 of 6	ENSP00000359911.1	Q9Y3L5
	RAP2C	ENST00000342983.6	TSL:1	c.466C>G	p.Leu156Val	missense	Exon 3 of 4	ENSP00000340274.2	Q9Y3L5
	RAP2C	ENST00000859955.1		c.466C>G	p.Leu156Val	missense	Exon 5 of 6	ENSP00000530014.1

Frequencies

GnomAD3 genomes AF: 0.000170 AC: 19 AN: 112093 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000617

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000491 AC: 9 AN: 183354 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000684

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: 0.0000173 AC: 19 AN: 1098122 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 5 AN XY: 363486

African (AFR) AF: 0.000720 AC: 19 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54143

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40531

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842032

Other (OTH) AF: 0.00 AC: 0 AN: 46092

GnomAD4 genome AF: 0.000170 AC: 19 AN: 112093 Hom.: 0 Cov.: 24 AF XY: 0.0000584 AC XY: 2 AN XY: 34263

African (AFR) AF: 0.000617 AC: 19 AN: 30810

American (AMR) AF: 0.00 AC: 0 AN: 10584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3588

South Asian (SAS) AF: 0.00 AC: 0 AN: 2717

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6075

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53232

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000253

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

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	0.19
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Uncertain	0.080
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.22	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	-0.99	N
PhyloP100		7.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.49	N
REVEL	Uncertain	0.39
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.56
MVP		0.86
MPC		1.2
ClinPred		0.14	T
GERP RS		5.6
Varity_R		0.40
gMVP		0.81
Mutation Taster		=96/4	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: rs371502735; hg19: chrX-131348282;