17-82032736-ATGG-A

Variant names:

• chr17-82032736-ATGG-A
• NM_005052.3:c.137_139delTGG

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PM4_Supporting

The NM_005052.3(RAC3):​c.137_139delTGG​(p.Val46del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RAC3 NM_005052.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.36

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
• PM4: Nonframeshift variant in NON repetitive region in NM_005052.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC3	NM_005052.3	c.137_139delTGG	p.Val46del	disruptive_inframe_deletion	Exon 3 of 6	ENST00000306897.9	NP_005043.1
RAC3	NM_001316307.2	c.137_139delTGG	p.Val46del	disruptive_inframe_deletion	Exon 3 of 6		NP_001303236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC3	ENST00000306897.9	c.137_139delTGG	p.Val46del	disruptive_inframe_deletion	Exon 3 of 6	1	NM_005052.3	ENSP00000304283.4
RAC3	ENST00000580965.5	c.5_7delTGG	p.Val2del	disruptive_inframe_deletion	Exon 2 of 5	2		ENSP00000463590.1
RAC3	ENST00000584341.1	c.5_7delTGG	p.Val2del	disruptive_inframe_deletion	Exon 2 of 5	5		ENSP00000462421.1
RAC3	ENST00000585014.1	n.-141_-139delTGG		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies Uncertain:1

May 22, 2022

3billion

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is not observed in the gnomAD v2.1.1 dataset. Inframe deletion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function. Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

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: chr17-79990612;