Variant chr3-133828795-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016577.4(RAB6B):c.620C>T(p.Ser207Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,611,374 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

RAB6B
NM_016577.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.53

Variant links:

Genes affected

RAB6B (HGNC:14902): (RAB6B, member RAS oncogene family) Enables myosin V binding activity. Predicted to be involved in Golgi vesicle transport; intracellular protein transport; and retrograde transport, endosome to Golgi. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

RAB6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022427142).

BS2

High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB6B	NM_016577.4 linkuse as main transcript	c.620C>T	p.Ser207Phe	missense_variant	8/8	ENST00000285208.9
RAB6B	NM_001363953.1 linkuse as main transcript	c.581C>T	p.Ser194Phe	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB6B	ENST00000285208.9 linkuse as main transcript	c.620C>T	p.Ser207Phe	missense_variant	8/8	1	NM_016577.4	P1	Q9NRW1-1
RAB6B	ENST00000543906.5 linkuse as main transcript	c.620C>T	p.Ser207Phe	missense_variant	8/9	1		P1	Q9NRW1-1
RAB6B	ENST00000486858.5 linkuse as main transcript	c.581C>T	p.Ser194Phe	missense_variant	9/9	2			Q9NRW1-2
RAB6B	ENST00000469959.1 linkuse as main transcript	c.96-810C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000596

AC:

148

AN:

248490

Hom.:

AF XY:

0.000543

AC XY:

AN XY:

134552

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000933

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.00123

AC:

1796

AN:

1459212

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

826

AN XY:

726086

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000756

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.000677

AC:

103

AN:

152162

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000733

Hom.:

Bravo

AF:

0.000638

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000453

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.000948

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

Mar 29, 2023

The c.620C>T (p.S207F) alteration is located in exon 8 (coding exon 8) of the RAB6B gene. This alteration results from a C to T substitution at nucleotide position 620, causing the serine (S) at amino acid position 207 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

0.32

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

.;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Uncertain

0.31

Sift

Benign

0.033

D;D;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.016

B;B;.

Vest4

0.45

MVP

0.35

MPC

0.43

ClinPred

0.11

GERP RS

6.1

Varity_R

0.62

gMVP

0.51

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