Variant 17-82658062-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006822.3(RAB40B):c.638C>T(p.Pro213Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RAB40B
NM_006822.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

Variant links:

Genes affected

RAB40B (HGNC:18284): (RAB40B, member RAS oncogene family) The protein encoded by this gene has similarity to a yeast protein which suggests a role of the gene product in regulating secretory vesicles. [provided by RefSeq, Jul 2008]

RAB40B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB40B	NM_006822.3 linkuse as main transcript	c.638C>T	p.Pro213Leu	missense_variant	6/6	ENST00000571995.6	NP_006813.1	Q12829
RAB40B	XM_011523528.3 linkuse as main transcript	c.587C>T	p.Pro196Leu	missense_variant	6/6		XP_011521830.1
RAB40B	XM_006722271.4 linkuse as main transcript	c.518C>T	p.Pro173Leu	missense_variant	6/6		XP_006722334.1
RAB40B	XM_017024042.2 linkuse as main transcript	c.458C>T	p.Pro153Leu	missense_variant	6/6		XP_016879531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40B	ENST00000571995.6 linkuse as main transcript	c.638C>T	p.Pro213Leu	missense_variant	6/6	1	NM_006822.3	ENSP00000461785.1		Q12829

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251468

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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 25, 2024

The c.638C>T (p.P213L) alteration is located in exon 6 (coding exon 6) of the RAB40B gene. This alteration results from a C to T substitution at nucleotide position 638, causing the proline (P) at amino acid position 213 to be replaced by a leucine (L). 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

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Uncertain

0.011

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.56

REVEL

Uncertain

0.59

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.47

MutPred

0.73

Loss of sheet (P = 0.0037);.;

MVP

0.85

MPC

1.2

ClinPred

0.97

GERP RS

4.8

Varity_R

0.39

gMVP

0.77

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