17-82032754-G-T

Variant names:

• chr17-82032754-G-T
• NM_005052.3:c.151G>T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_005052.3(RAC3):​c.151G>T​(p.Val51Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RAC3 NM_005052.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.24

Genes affected

RAC3 (HGNC:9803): (Rac family small GTPase 3) The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a chain Ras-related C3 botulinum toxin substrate 3 (size 188) in uniprot entity RAC3_HUMAN there are 14 pathogenic changes around while only 1 benign (93%) in NM_005052.3
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC3	NM_005052.3	c.151G>T	p.Val51Phe	missense_variant	Exon 3 of 6	ENST00000306897.9	NP_005043.1
RAC3	NM_001316307.2	c.151G>T	p.Val51Phe	missense_variant	Exon 3 of 6		NP_001303236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC3	ENST00000306897.9	c.151G>T	p.Val51Phe	missense_variant	Exon 3 of 6	1	NM_005052.3	ENSP00000304283.4
RAC3	ENST00000580965.5	c.19G>T	p.Val7Phe	missense_variant	Exon 2 of 5	2		ENSP00000463590.1
RAC3	ENST00000584341.1	c.19G>T	p.Val7Phe	missense_variant	Exon 2 of 5	5		ENSP00000462421.1
RAC3	ENST00000585014.1	n.-124G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151G>T (p.V51F) alteration is located in exon 3 (coding exon 3) of the RAC3 gene. This alteration results from a G to T substitution at nucleotide position 151, causing the valine (V) at amino acid position 51 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D;D;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Pathogenic	0.39	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Uncertain	0.022	D
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.5	D;.;.
REVEL	Pathogenic	0.73
Sift	Benign	0.037	D;.;.
Sift4G	Benign	0.098	T;T;T
Polyphen		0.015	B;.;.
Vest4		0.91
MutPred		0.54		Gain of catalytic residue at V51 (P = 0.1381);.;.;
MVP		0.91
MPC		1.3
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.87

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79990630;