chr2-237578033-C-A

Variant names:

• chr2-237578033-C-A
• rs775784513
• NM_022449.4:c.280G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022449.4(RAB17):​c.280G>T​(p.Ala94Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RAB17 NM_022449.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53
• Publications: 1 publications found

Genes affected

RAB17 (HGNC:16523): (RAB17, member RAS oncogene family) The Rab subfamily of small GTPases plays an important role in the regulation of membrane trafficking. RAB17 is an epithelial cell-specific GTPase (Lutcke et al., 1993 [PubMed 8486736]).[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022449.4. 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
	RAB17	NM_022449.4	MANE Select	c.280G>T	p.Ala94Ser	missense	Exon 3 of 6	NP_071894.1	Q9H0T7-1
	RAB17	NR_033308.2		n.429-651G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB17	ENST00000264601.8	TSL:1 MANE Select	c.280G>T	p.Ala94Ser	missense	Exon 3 of 6	ENSP00000264601.3	Q9H0T7-1
	RAB17	ENST00000477149.5	TSL:1	n.1538G>T		non_coding_transcript_exon	Exon 1 of 3
	RAB17	ENST00000392001.6	TSL:1	n.158-651G>T		intron	N/A	ENSP00000375858.2	F8WAG1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250624 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

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	0.32
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		7.5
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.75	P
Vest4		0.60
MutPred		0.69		Loss of stability (P = 0.0922)
MVP		0.87
MPC		0.42
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.46
gMVP		0.54
Mutation Taster		=46/54	disease causing

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: rs775784513; hg19: chr2-238486676;