Variant 11-88114118-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022337.3(RAB38):c.506C>G(p.Ala169Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RAB38
NM_022337.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

RAB38 (HGNC:9776): (RAB38, member RAS oncogene family) Enables several functions, including AP-1 adaptor complex binding activity; AP-3 adaptor complex binding activity; and BLOC-2 complex binding activity. Involved in several processes, including endosome to melanosome transport; melanosome assembly; and phagosome acidification. Located in several cellular components, including cytoplasmic vesicle; lysosome; and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB38 links:

ENSG00000255241 (HGNC:):

ENSG00000255241 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB38	NM_022337.3 linkuse as main transcript	c.506C>G	p.Ala169Gly	missense_variant	3/3	ENST00000243662.11	NP_071732.1	P57729A0A024R191
RAB38	XM_017017455.3 linkuse as main transcript	c.483+35557C>G		intron_variant			XP_016872944.1
RAB38	XM_017017456.3 linkuse as main transcript	c.483+35557C>G		intron_variant			XP_016872945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB38	ENST00000243662.11 linkuse as main transcript	c.506C>G	p.Ala169Gly	missense_variant	3/3	1	NM_022337.3	ENSP00000243662.5	P57729
RAB38	ENST00000526372.1 linkuse as main transcript	c.500C>G	p.Ala167Gly	missense_variant	3/3	3		ENSP00000433317.1	H0YDB7
RAB38	ENST00000531138.1 linkuse as main transcript	c.*6C>G		3_prime_UTR_variant	2/2	2		ENSP00000435340.1	H0YEA4
ENSG00000255241	ENST00000528458.1 linkuse as main transcript	n.139-1355G>C		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

8.99e-7

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

May 03, 2023

The c.506C>G (p.A169G) alteration is located in exon 3 (coding exon 3) of the RAB38 gene. This alteration results from a C to G substitution at nucleotide position 506, causing the alanine (A) at amino acid position 169 to be replaced by a glycine (G). 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

Uncertain

0.34

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.40

MutationAssessor

Pathogenic

2.9

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.63

Sift

Benign

0.063

Sift4G

Uncertain

0.034

Polyphen

0.97

Vest4

0.56

MutPred

0.80

Loss of stability (P = 0.0358);

MVP

0.91

MPC

0.22

ClinPred

0.99

GERP RS

5.5

Varity_R

0.85

gMVP

0.62

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over