Genetic Variant NM_022449.4:c.38C>T (chr2-237586117-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022449.4(RAB17):c.38C>T(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RAB17
NM_022449.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0350

Publications

0 publications found

Variant links:

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]

RAB17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.076415926).

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.38C>T	p.Ala13Val	missense	Exon 2 of 6	NP_071894.1	Q9H0T7-1
	RAB17	NR_033308.2		n.309C>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB17	ENST00000264601.8	TSL:1 MANE Select	c.38C>T	p.Ala13Val	missense	Exon 2 of 6	ENSP00000264601.3	Q9H0T7-1
RAB17	ENST00000392001.6	TSL:1	n.38C>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000375858.2	F8WAG1
RAB17	ENST00000904317.1		c.38C>T	p.Ala13Val	missense	Exon 2 of 7	ENSP00000574376.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458382

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.00

AC:

AN:

44202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39462

South Asian (SAS)

AF:

0.00

AC:

AN:

85746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110480

Other (OTH)

AF:

0.0000166

AC:

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.2

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.50

M_CAP

Benign

0.017

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.035

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.5

REVEL

Benign

0.012

Sift

Benign

0.067

Sift4G

Benign

0.10

Polyphen

0.027

Vest4

0.097

MutPred

0.26

Gain of loop (P = 0.0312)

MVP

0.24

MPC

0.12

ClinPred

0.058

GERP RS

1.7

PromoterAI

0.0096

Neutral

(source)

Varity_R

0.028

gMVP

0.26

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over