Variant 14-64971977-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001308154.2(RAB15):c.100C>T(p.His34Tyr) 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: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB15
NM_001308154.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

RAB15 (HGNC:20150): (RAB15, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in positive regulation of regulated secretory pathway. Located in cilium; endosome membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB15 links:

CHURC1-FNTB (HGNC:):

CHURC1-FNTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3719499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB15	NM_001308154.2 linkuse as main transcript	c.100C>T	p.His34Tyr	missense_variant	1/7	ENST00000533601.7	NP_001295083.1
CHURC1-FNTB	NM_001202559.1 linkuse as main transcript	c.328-32272G>A		intron_variant			NP_001189488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB15	ENST00000533601.7 linkuse as main transcript	c.100C>T	p.His34Tyr	missense_variant	1/7	1	NM_001308154.2	ENSP00000434103	P1	P59190-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000456

AC:

AN:

219064

Hom.:

AF XY:

0.00

AC XY:

AN XY:

118436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000139

AC:

AN:

1443250

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716308

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.100C>T (p.H34Y) alteration is located in exon 1 (coding exon 1) of the RAB15 gene. This alteration results from a C to T substitution at nucleotide position 100, causing the histidine (H) at amino acid position 34 to be replaced by a tyrosine (Y). 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

0.23

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

.;D;.;.

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.051

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.37

T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

-0.62

N;N;.;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.6

D;D;.;.

REVEL

Benign

0.28

Sift

Benign

0.19

T;D;.;.

Sift4G

Uncertain

0.050

T;D;.;.

Polyphen

0.89

P;.;.;.

Vest4

0.29

MutPred

0.27

Loss of disorder (P = 0.0245);Loss of disorder (P = 0.0245);.;.;

MVP

0.88

MPC

1.2

ClinPred

0.44

GERP RS

2.4

Varity_R

0.66

gMVP

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over