rs200877853

Variant names:

• chrX-130172099-C-T
• rs200877853
• NM_004794.3:c.37C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004794.3(RAB33A):​c.37C>T​(p.Pro13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,209,925 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 3 hem.)
• Consequence: RAB33A NM_004794.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024344683).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004794.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB33A	NM_004794.3	MANE Select	c.37C>T	p.Pro13Ser	missense	Exon 1 of 2	NP_004785.1	Q14088

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB33A	ENST00000257017.5	TSL:1 MANE Select	c.37C>T	p.Pro13Ser	missense	Exon 1 of 2	ENSP00000257017.4	Q14088
	RAB33A	ENST00000970517.1		c.37C>T	p.Pro13Ser	missense	Exon 1 of 2	ENSP00000640576.1

Frequencies

GnomAD3 genomes AF: 0.0000709 AC: 8 AN: 112760 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000337 AC: 6 AN: 178256 AF XY: 0.0000469

Gnomad AFR exome AF: 0.000394

Gnomad AMR exome AF: 0.0000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000456 AC: 5 AN: 1097113 Hom.: 0 Cov.: 31 AF XY: 0.00000827 AC XY: 3 AN XY: 362667

African (AFR) AF: 0.000152 AC: 4 AN: 26377

American (AMR) AF: 0.00 AC: 0 AN: 35127

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19341

East Asian (EAS) AF: 0.00 AC: 0 AN: 30171

South Asian (SAS) AF: 0.00 AC: 0 AN: 54011

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40239

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841663

Other (OTH) AF: 0.00 AC: 0 AN: 46051

GnomAD4 genome AF: 0.0000709 AC: 8 AN: 112812 Hom.: 0 Cov.: 24 AF XY: 0.0000572 AC XY: 2 AN XY: 34976

African (AFR) AF: 0.000257 AC: 8 AN: 31181

American (AMR) AF: 0.00 AC: 0 AN: 10824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3514

South Asian (SAS) AF: 0.00 AC: 0 AN: 2789

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6245

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53159

Other (OTH) AF: 0.00 AC: 0 AN: 1548

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000756

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.074
Sift	Benign	0.20	T
Sift4G	Benign	0.83	T
Polyphen		0.0010	B
Vest4		0.16
MVP		0.44
MPC		1.1
ClinPred		0.039	T
GERP RS		3.3
PromoterAI		-0.024	Neutral
Varity_R		0.059
gMVP		0.49
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs200877853; hg19: chrX-129306073;