12-48865673-A-C

Variant names:

• chr12-48865673-A-C
• NM_014470.4:c.95T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014470.4(RND1):​c.95T>G​(p.Val32Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RND1 NM_014470.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09
• Publications: 0 publications found

Genes affected

RND1 (HGNC:18314): (Rho family GTPase 1) This gene encodes a protein that belongs to the Rho GTPase family. Members of this family regulate the organization of the actin cytoskeleton in response to extracellular growth factors. A similar protein in rat interacts with a microtubule regulator to control axon extension. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014470.4. 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
	RND1	NM_014470.4	MANE Select	c.95T>G	p.Val32Gly	missense	Exon 1 of 5	NP_055285.1	Q92730

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RND1	ENST00000309739.6	TSL:1 MANE Select	c.95T>G	p.Val32Gly	missense	Exon 1 of 5	ENSP00000308461.5	Q92730
	RND1	ENST00000551243.1	TSL:3	n.95T>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000449045.1	F8VXU4
	RND1	ENST00000649147.1		n.198T>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.50		Gain of catalytic residue at Q31 (P = 0)
MVP		0.94
MPC		1.7
ClinPred		1.0	D
GERP RS		4.9
PromoterAI		-0.041	Neutral
Varity_R		0.96
gMVP		0.76
Mutation Taster		=6/94	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr12-49259456;