rs1274238232

Variant names:

• chrX-130184328-G-C
• rs1274238232
• NM_004794.3:c.302G>C

Variant summary

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

The NM_004794.3(RAB33A):​c.302G>C​(p.Ser101Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,912 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: RAB33A NM_004794.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.32

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB33A	NM_004794.3	c.302G>C	p.Ser101Thr	missense_variant	Exon 2 of 2	ENST00000257017.5	NP_004785.1
RAB33A	XM_017029963.3	c.74G>C	p.Ser25Thr	missense_variant	Exon 3 of 3		XP_016885452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB33A	ENST00000257017.5	c.302G>C	p.Ser101Thr	missense_variant	Exon 2 of 2	1	NM_004794.3	ENSP00000257017.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000165 AC: 3 AN: 182239 Hom.: 0 AF XY: 0.0000149 AC XY: 1 AN XY: 66989

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000216

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097912 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363280

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000662

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302G>C (p.S101T) alteration is located in exon 2 (coding exon 2) of the RAB33A gene. This alteration results from a G to C substitution at nucleotide position 302, causing the serine (S) at amino acid position 101 to be replaced by a threonine (T). 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	0.49
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.39	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.71	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.47
Sift	Benign	0.65	T
Sift4G	Benign	0.47	T
Polyphen		0.90	P
Vest4		0.43
MutPred		0.62		Loss of disorder (P = 0.0805);
MVP		0.85
MPC		1.1
ClinPred		0.29	T
GERP RS		3.8
Varity_R		0.74
gMVP		0.90

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

LitVar

Other links and lift over

dbSNP: rs1274238232; hg19: chrX-129318302;