17-82033443-T-C

Position:

• chr17-82033443-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005052.3(RAC3):​c.292T>C​(p.Tyr98His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAC3 NM_005052.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC3	NM_005052.3	c.292T>C	p.Tyr98His	missense_variant	5/6	ENST00000306897.9	NP_005043.1
RAC3	NM_001316307.2	c.292T>C	p.Tyr98His	missense_variant	5/6		NP_001303236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC3	ENST00000306897.9	c.292T>C	p.Tyr98His	missense_variant	5/6	1	NM_005052.3	ENSP00000304283	P1
RAC3	ENST00000580965.5	c.160T>C	p.Tyr54His	missense_variant	4/5	2		ENSP00000463590
RAC3	ENST00000584341.1	c.160T>C	p.Tyr54His	missense_variant	4/5	5		ENSP00000462421
RAC3	ENST00000585014.1	n.136T>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.292T>C (p.Y98H) alteration is located in exon 5 (coding exon 5) of the RAC3 gene. This alteration results from a T to C substitution at nucleotide position 292, causing the tyrosine (Y) at amino acid position 98 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.76	D;D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.0045
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.3	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.5	D;.;.
REVEL	Uncertain	0.45
Sift	Benign	0.27	T;.;.
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.80
MutPred		0.51		Gain of disorder (P = 0.0191);.;.;
MVP		0.76
MPC		0.95
ClinPred		0.79	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-79991319;