Variant 18-9708442-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006868.4(RAB31):c.37G>A(p.Gly13Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000282 in 1,416,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RAB31
NM_006868.4 missense, splice_region

Scores

Splicing: ADA: 0.1176

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

Genes affected

RAB31 (HGNC:9771): (RAB31, member RAS oncogene family) Enables GDP binding activity and GTP binding activity. Involved in several processes, including Golgi to plasma membrane protein transport; cellular response to insulin stimulus; and receptor internalization. Located in early endosome; phagocytic vesicle; and trans-Golgi network membrane. Biomarker of severe acute respiratory syndrome. [provided by Alliance of Genome Resources, Apr 2022]

RAB31 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB31	NM_006868.4 linkuse as main transcript	c.37G>A	p.Gly13Arg	missense_variant, splice_region_variant	1/7	ENST00000578921.6	NP_006859.2	Q13636

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB31	ENST00000578921.6 linkuse as main transcript	c.37G>A	p.Gly13Arg	missense_variant, splice_region_variant	1/7	1	NM_006868.4	ENSP00000461945.2	Q13636
RAB31	ENST00000578734.5 linkuse as main transcript	n.37G>A		splice_region_variant, non_coding_transcript_exon_variant	1/6	3		ENSP00000462164.2	J3KRU3
RAB31	ENST00000581109.1 linkuse as main transcript	n.37G>A		splice_region_variant, non_coding_transcript_exon_variant	1/5	3		ENSP00000464046.2	J3QR51
RAB31	ENST00000583137.1 linkuse as main transcript	n.37G>A		splice_region_variant, non_coding_transcript_exon_variant	1/5	3		ENSP00000462561.2	J3KSM8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000500

AC:

AN:

200082

Hom.:

AF XY:

0.00

AC XY:

AN XY:

111800

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:

0.0000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1416958

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704720

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:

0.00000367

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000168

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

Nov 13, 2024

The c.37G>A (p.G13R) alteration is located in exon 1 (coding exon 1) of the RAB31 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the glycine (G) at amino acid position 13 to be replaced by an arginine (R). 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

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.57

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.92

M_CAP

Pathogenic

0.96

MetaRNN

Pathogenic

0.95

MetaSVM

Pathogenic

0.83

PrimateAI

Pathogenic

0.95

Sift4G

Pathogenic

0.0

Vest4

0.86

MVP

0.96

MPC

1.4

ClinPred

0.99

GERP RS

4.5

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.12

dbscSNV1_RF

Benign

0.43

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