7-6391938-CT-AC

Position:

• chr7-6391938-CT-AC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3 PP5

The NM_006908.5(RAC1):​c.122_123delCTinsAC​(p.Ser41Tyr) variant causes a missense 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 Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAC1 NM_006908.5 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.90

Genes affected

RAC1 (HGNC:9801): (Rac family small GTPase 1) 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

RAC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RAC1. . Gene score misZ 3.1347 (greater than the threshold 3.09). Trascript score misZ 3.9366 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 48.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 7-6391938-CT-AC is Pathogenic according to our data. Variant chr7-6391938-CT-AC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2577934.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC1	NM_006908.5	c.122_123delCTinsAC	p.Ser41Tyr	missense_variant		ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.122_123delCTinsAC	p.Ser41Tyr	missense_variant			NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.122_123delCTinsAC	p.Ser41Tyr	missense_variant		1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Molecular Genetics laboratory, Necker Hospital

Apr 26, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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: chr7-6431569;