Variant 11-82982386-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286060.2(RAB30):c.391G>C(p.Glu131Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 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: 6.8e-7 ( 0 hom. )

Consequence

RAB30
NM_001286060.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

Variant links:

Genes affected

RAB30 (HGNC:9770): (RAB30, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in Golgi organization. Located in Golgi cisterna; cis-Golgi network; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

RAB30 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17846489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAB30	NM_001286060.2 linkuse as main transcript	c.391G>C	p.Glu131Gln	missense_variant	5/5	ENST00000527633.6	NP_001272989.1
RAB30	NM_001286059.2 linkuse as main transcript	c.391G>C	p.Glu131Gln	missense_variant	5/5		NP_001272988.1
RAB30	NM_001286061.1 linkuse as main transcript	c.391G>C	p.Glu131Gln	missense_variant	5/5		NP_001272990.1
RAB30	NM_014488.5 linkuse as main transcript	c.391G>C	p.Glu131Gln	missense_variant	6/6		NP_055303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB30	ENST00000527633.6 linkuse as main transcript	c.391G>C	p.Glu131Gln	missense_variant	5/5	1	NM_001286060.2	ENSP00000435089	P1	Q15771-1
	ENST00000527550.1 linkuse as main transcript	n.373-18645G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251326

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

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:

6.84e-7

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Jul 14, 2023

The c.391G>C (p.E131Q) alteration is located in exon 6 (coding exon 4) of the RAB30 gene. This alteration results from a G to C substitution at nucleotide position 391, causing the glutamic acid (E) at amino acid position 131 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.24

M_CAP

Benign

0.024

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.58

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Benign

-0.090

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.19

Vest4

0.13

MutPred

0.29

Loss of methylation at K127 (P = 0.0745);

MVP

0.65

ClinPred

0.23

GERP RS

6.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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