17-82658107-C-T

Position:

• chr17-82658107-C-T

Variant summary

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

The NM_006822.3(RAB40B):​c.593G>A​(p.Arg198Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,788 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: 0.000014 (0 hom.)
• Consequence: RAB40B NM_006822.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85

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]

ACMG classification

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	c.593G>A	p.Arg198Gln	missense_variant	6/6	ENST00000571995.6	NP_006813.1
RAB40B	XM_011523528.3	c.542G>A	p.Arg181Gln	missense_variant	6/6		XP_011521830.1
RAB40B	XM_006722271.4	c.473G>A	p.Arg158Gln	missense_variant	6/6		XP_006722334.1
RAB40B	XM_017024042.2	c.413G>A	p.Arg138Gln	missense_variant	6/6		XP_016879531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40B	ENST00000571995.6	c.593G>A	p.Arg198Gln	missense_variant	6/6	1	NM_006822.3	ENSP00000461785.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461788 Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10 AN XY: 727196

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.593G>A (p.R198Q) alteration is located in exon 6 (coding exon 6) of the RAB40B gene. This alteration results from a G to A substitution at nucleotide position 593, causing the arginine (R) at amino acid position 198 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	0.21
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.60	T
REVEL	Benign	0.27
Sift4G	Uncertain	0.048	D;T
Polyphen		0.99	D;.
Vest4		0.27
MutPred		0.56		Loss of sheet (P = 0.0126);.;
MVP		0.67
MPC		1.3
ClinPred		0.93	D
GERP RS		3.8
Varity_R		0.19
gMVP		0.67

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

Other links and lift over

dbSNP: rs1407483597; hg19: chr17-80615983;