Variant chr2-129980339-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032144.3(RAB6C):c.224T>A(p.Leu75His) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB6C
NM_032144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

RAB6C (HGNC:16525): (RAB6C, member RAS oncogene family) Enables GTPase activity. Involved in mitotic cell cycle; regulation of centrosome duplication; and response to xenobiotic stimulus. Located in Golgi apparatus and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

RAB6C links:

RAB6C-AS1 (HGNC:49278): (RAB6C antisense RNA 1)

RAB6C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.116413236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB6C	NM_032144.3 linkuse as main transcript	c.224T>A	p.Leu75His	missense_variant	1/1	ENST00000410061.4	NP_115520.2
RAB6C-AS1	NR_036537.1 linkuse as main transcript	n.134A>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RAB6C	ENST00000410061.4 linkuse as main transcript	c.224T>A	p.Leu75His	missense_variant	1/1		NM_032144.3	ENSP00000387307	P1
RAB6C-AS1	ENST00000412425.1 linkuse as main transcript	n.128A>T		non_coding_transcript_exon_variant	1/6	1
RAB6C-AS1	ENST00000624615.1 linkuse as main transcript	n.74A>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000306

AC:

AN:

150446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000840

AC:

AN:

238054

Hom.:

AF XY:

0.0000695

AC XY:

AN XY:

129568

show subpopulations

Gnomad AFR exome

AF:

0.000965

Gnomad AMR exome

AF:

0.000118

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:

0.00

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000336

AC:

AN:

1459924

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726140

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.000134

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000306

AC:

AN:

150538

Hom.:

Cov.:

AF XY:

0.000313

AC XY:

AN XY:

73482

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

ESP6500AA

AF:

0.000701

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000908

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

Jan 09, 2024

The c.224T>A (p.L75H) alteration is located in exon 1 (coding exon 1) of the RAB6C gene. This alteration results from a T to A substitution at nucleotide position 224, causing the leucine (L) at amino acid position 75 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.17

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.44

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.1

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.92

Vest4

0.33

MVP

0.78

ClinPred

0.12

Varity_R

0.27

gMVP

0.083

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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