NM_005052.3:c.12C>T

Variant names:

• chr17-82031773-C-T
• NM_005052.3:c.12C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_005052.3(RAC3):​c.12C>T​(p.Ile4Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 849,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: RAC3 NM_005052.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.483
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with structural brain anomalies and dysmorphic facies

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 17-82031773-C-T is Benign according to our data. Variant chr17-82031773-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3026793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.483 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005052.3. 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
	RAC3	NM_005052.3	MANE Select	c.12C>T	p.Ile4Ile	synonymous	Exon 1 of 6	NP_005043.1	P60763
	RAC3	NM_001316307.2		c.12C>T	p.Ile4Ile	synonymous	Exon 1 of 6	NP_001303236.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC3	ENST00000306897.9	TSL:1 MANE Select	c.12C>T	p.Ile4Ile	synonymous	Exon 1 of 6	ENSP00000304283.4	P60763
	RAC3	ENST00000924839.1		c.12C>T	p.Ile4Ile	synonymous	Exon 1 of 6	ENSP00000594898.1
	RAC3	ENST00000924841.1		c.12C>T	p.Ile4Ile	synonymous	Exon 1 of 6	ENSP00000594900.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 849548 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 395556

African (AFR) AF: 0.00 AC: 0 AN: 15988

American (AMR) AF: 0.00 AC: 0 AN: 1496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4142

South Asian (SAS) AF: 0.00 AC: 0 AN: 18508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1676

European-Non Finnish (NFE) AF: 0.00000129 AC: 1 AN: 773152

Other (OTH) AF: 0.00 AC: 0 AN: 28034

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.99
PhyloP100		-0.48
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: chr17-79989649;