Variant 17-82032956-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_005052.3(RAC3):c.235C>T(p.Leu79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,762 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000021 ( 2 hom. )

Consequence

RAC3
NM_005052.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 17-82032956-C-T is Benign according to our data. Variant chr17-82032956-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3034130.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC3	NM_005052.3 linkuse as main transcript	c.235C>T	p.Leu79=	synonymous_variant	4/6	ENST00000306897.9	NP_005043.1
RAC3	NM_001316307.2 linkuse as main transcript	c.235C>T	p.Leu79=	synonymous_variant	4/6		NP_001303236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RAC3	ENST00000306897.9 linkuse as main transcript	c.235C>T	p.Leu79=	synonymous_variant	4/6	1	NM_005052.3	ENSP00000304283	P1
RAC3	ENST00000580965.5 linkuse as main transcript	c.103C>T	p.Leu35=	synonymous_variant	3/5	2		ENSP00000463590
RAC3	ENST00000584341.1 linkuse as main transcript	c.103C>T	p.Leu35=	synonymous_variant	3/5	5		ENSP00000462421
RAC3	ENST00000585014.1 linkuse as main transcript	n.79C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250896

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.000496

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000212

AC:

AN:

1461388

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000177

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000185

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAC3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over