X-130172070-A-C

Position:

• chrX-130172070-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004794.3(RAB33A):​c.8A>C​(p.Gln3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: RAB33A NM_004794.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.704

Genes affected

RAB33A (HGNC:9773): (RAB33A, member RAS oncogene family) The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. It is GTP-binding protein and may be involved in vesicle transport. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19440198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB33A	NM_004794.3	c.8A>C	p.Gln3Pro	missense_variant	1/2	ENST00000257017.5
RAB33A	XM_017029963.3	c.31-12215A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB33A	ENST00000257017.5	c.8A>C	p.Gln3Pro	missense_variant	1/2	1	NM_004794.3	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.8A>C (p.Q3P) alteration is located in exon 1 (coding exon 1) of the RAB33A gene. This alteration results from a A to C substitution at nucleotide position 8, causing the glutamine (Q) at amino acid position 3 to be replaced by a proline (P). 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	Benign	0.069
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.97	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Polyphen		0.32	B
Vest4		0.32
MutPred		0.20		Gain of glycosylation at Q3 (P = 0.0573);
MVP		0.98
MPC		1.3
ClinPred		0.28	T
GERP RS		5.2
Varity_R		0.34
gMVP		0.67

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: chrX-129306044;