Variant 17-82032796-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_005052.3(RAC3):c.193G>A(p.Asp65Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAC3
NM_005052.3 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.59

Variant links:

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]

RAC3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

PP5

Variant 17-82032796-G-A is Pathogenic according to our data. Variant chr17-82032796-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3347558.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC3	NM_005052.3 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	3/6	ENST00000306897.9	NP_005043.1	P60763
RAC3	NM_001316307.2 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	3/6		NP_001303236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAC3	ENST00000306897.9 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	3/6	1	NM_005052.3	ENSP00000304283.4	P60763
RAC3	ENST00000580965.5 linkuse as main transcript	c.61G>A	p.Asp21Asn	missense_variant	2/5	2		ENSP00000463590.1	J3QLK0
RAC3	ENST00000584341.1 linkuse as main transcript	c.61G>A	p.Asp21Asn	missense_variant	2/5	5		ENSP00000462421.1	J3KSC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460698

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAC3-related disorder

Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2024

The RAC3 c.193G>A variant is predicted to result in the amino acid substitution p.Asp65Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is interpreted as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

D;D;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.7

D;.;.

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

D;.;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.88

P;.;.

Vest4

0.83

MutPred

0.51

Gain of helix (P = 0.0854);.;.;

MVP

0.87

MPC

1.3

ClinPred

1.0

GERP RS

3.8

Varity_R

0.84

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over