Variant 19-40780496-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_016154.5(RAB4B):c.209T>G(p.Phe70Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.00044 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB4B
NM_016154.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

Variant links:

Genes affected

RAB4B (HGNC:9782): (RAB4B, member RAS oncogene family) Predicted to enable G protein activity and GTP binding activity. Involved in glucose import. Located in insulin-responsive compartment; perinuclear region of cytoplasm; and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

RAB4B links:

MIA-RAB4B (HGNC:):

MIA-RAB4B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.971

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAB4B	NM_016154.5 linkuse as main transcript	c.209T>G	p.Phe70Cys	missense_variant	3/8	ENST00000357052.8	NP_057238.3
MIA-RAB4B	NR_037775.1 linkuse as main transcript	n.571T>G		non_coding_transcript_exon_variant	5/10
RAB4B-EGLN2	NR_037791.1 linkuse as main transcript	n.366T>G		non_coding_transcript_exon_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB4B	ENST00000357052.8 linkuse as main transcript	c.209T>G	p.Phe70Cys	missense_variant	3/8	1	NM_016154.5	ENSP00000349560	P1	P61018-1
	ENST00000595728.2 linkuse as main transcript	n.992-605A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000440

AC:

643

AN:

1460456

Hom.:

Cov.:

AF XY:

0.000424

AC XY:

308

AN XY:

726492

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000527

Gnomad4 OTH exome

AF:

0.000365

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 30, 2024

The c.209T>G (p.F70C) alteration is located in exon 3 (coding exon 3) of the RAB4B gene. This alteration results from a T to G substitution at nucleotide position 209, causing the phenylalanine (F) at amino acid position 70 to be replaced by a cysteine (C). 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

1.0

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.78

D;D

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

.;T

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

4.1

H;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-7.1

.;D

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.94

MutPred

0.88

Gain of catalytic residue at S72 (P = 0.0852);Gain of catalytic residue at S72 (P = 0.0852);

MVP

0.93

MPC

1.2

ClinPred

1.0

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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