Genetic Variant RAB30:p.Leu197Phe (chr11-82982186-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001286060.2(RAB30):c.591G>T(p.Leu197Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 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: 4.92

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:

ENSG00000254698 (HGNC:):

ENSG00000254698 links:

Genome browser will be placed here

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=0.18401596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB30	NM_001286060.2 link	c.591G>T	p.Leu197Phe	missense_variant	Exon 5 of 5	ENST00000527633.6	NP_001272989.1	Q15771-1A8K5R1
RAB30	NM_001286059.2 link	c.591G>T	p.Leu197Phe	missense_variant	Exon 5 of 5		NP_001272988.1	Q15771-1A8K5R1
RAB30	NM_001286061.1 link	c.591G>T	p.Leu197Phe	missense_variant	Exon 5 of 5		NP_001272990.1	Q15771-1A8K5R1
RAB30	NM_014488.5 link	c.591G>T	p.Leu197Phe	missense_variant	Exon 6 of 6		NP_055303.2	Q15771-1A8K5R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB30	ENST00000527633.6 link	c.591G>T	p.Leu197Phe	missense_variant	Exon 5 of 5	1	NM_001286060.2	ENSP00000435089.1		Q15771-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251074

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135664

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.591G>T (p.L197F) alteration is located in exon 6 (coding exon 4) of the RAB30 gene. This alteration results from a G to T substitution at nucleotide position 591, causing the leucine (L) at amino acid position 197 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.033

T;T;T;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.082

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;.;.;D;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;.;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.40

.;N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.13

.;T;T;T;T

Sift4G

Benign

0.63

T;T;T;T;T

Polyphen

0.080

B;B;B;.;B

Vest4

0.34

MutPred

0.33

Gain of methylation at K192 (P = 0.0775);Gain of methylation at K192 (P = 0.0775);Gain of methylation at K192 (P = 0.0775);.;Gain of methylation at K192 (P = 0.0775);

MVP

0.29

MPC

0.90

ClinPred

0.37

GERP RS

5.0

Varity_R

0.15

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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