rs1026908105

Variant names:

• chr17-82032381-C-G
• rs1026908105
• NM_005052.3:c.36-6C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-82032381-C-G
• chr17-82032381-C-A
• chr17-82032381-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005052.3(RAC3):​c.36-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
• Consequence: RAC3 NM_005052.3 splice_region, intron
• Scores: Splicing: ADA: 0.8949
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

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.36-6C>G		splice_region intron	N/A	NP_005043.1	P60763
	RAC3	NM_001316307.2		c.36-6C>G		splice_region intron	N/A	NP_001303236.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC3	ENST00000306897.9	TSL:1 MANE Select	c.36-6C>G		splice_region intron	N/A	ENSP00000304283.4	P60763
	RAC3	ENST00000924839.1		c.309C>G	p.Val103Val	synonymous	Exon 2 of 6	ENSP00000594898.1
	RAC3	ENST00000580965.5	TSL:2	c.-103C>G		5_prime_UTR	Exon 1 of 5	ENSP00000463590.1	J3QLK0

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74284

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	-0.47
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		2.3
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.31		Position offset: 6

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

Other links and lift over

dbSNP: rs1026908105; hg19: chr17-79990257;