chrX-132214200-C-A

Variant names:

• chrX-132214200-C-A
• NM_001271186.2:c.520G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271186.2(RAP2C):​c.520G>T​(p.Asp174Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D174G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: RAP2C NM_001271186.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35685998).

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.520G>T	p.Asp174Tyr	missense	Exon 5 of 6	NP_001258115.1	Q9Y3L5
	RAP2C	NM_021183.5		c.520G>T	p.Asp174Tyr	missense	Exon 3 of 4	NP_067006.3
	RAP2C	NM_001271187.2		c.322G>T	p.Asp108Tyr	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.520G>T	p.Asp174Tyr	missense	Exon 5 of 6	ENSP00000359911.1	Q9Y3L5
	RAP2C	ENST00000342983.6	TSL:1	c.520G>T	p.Asp174Tyr	missense	Exon 3 of 4	ENSP00000340274.2	Q9Y3L5
	RAP2C	ENST00000859955.1		c.520G>T	p.Asp174Tyr	missense	Exon 5 of 6	ENSP00000530014.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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	0.17
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.23
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.010	D
Polyphen		0.68	P
Vest4		0.41
MutPred		0.38		Loss of disorder (P = 0.0343)
MVP		0.98
MPC		1.5
ClinPred		0.91	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.70
Mutation Taster		=54/46	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

hg19: chrX-131348228;