Variant 6-57196617-ACAATCAATCAAT-ACAATCAATCAATCAAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The ENST00000468148.6(RAB23):c.242-12_242-11insATTG variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,612,268 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 20 hom. )

Consequence

RAB23
ENST00000468148.6 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

RAB23 (HGNC:14263): (RAB23, member RAS oncogene family) This gene encodes a small GTPase of the Ras superfamily. Rab proteins are involved in the regulation of diverse cellular functions associated with intracellular membrane trafficking, including autophagy and immune response to bacterial infection. The encoded protein may play a role in central nervous system development by antagonizing sonic hedgehog signaling. Disruption of this gene has been implicated in Carpenter syndrome as well as cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RAB23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 6-57196617-A-ACAAT is Benign according to our data. Variant chr6-57196617-A-ACAAT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 357645.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00362 (551/152296) while in subpopulation AMR AF= 0.00542 (83/15300). AF 95% confidence interval is 0.00487. There are 0 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB23	NM_016277.5 linkuse as main transcript	c.242-12_242-11insATTG		splice_polypyrimidine_tract_variant, intron_variant		ENST00000468148.6	NP_057361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB23	ENST00000468148.6 linkuse as main transcript	c.242-12_242-11insATTG		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016277.5	ENSP00000417610	P1
RAB23	ENST00000317483.4 linkuse as main transcript	c.242-12_242-11insATTG		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000320413	P1

Frequencies

GnomAD3 genomes

AF:

0.00362

AC:

551

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00532

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00331

AC:

808

AN:

244302

Hom.:

AF XY:

0.00342

AC XY:

452

AN XY:

132180

show subpopulations

Gnomad AFR exome

AF:

0.000571

Gnomad AMR exome

AF:

0.00288

Gnomad ASJ exome

AF:

0.00646

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00384

Gnomad FIN exome

AF:

0.00131

Gnomad NFE exome

AF:

0.00431

Gnomad OTH exome

AF:

0.00333

GnomAD4 exome

AF:

0.00534

AC:

7802

AN:

1459972

Hom.:

Cov.:

AF XY:

0.00522

AC XY:

3792

AN XY:

726192

show subpopulations

Gnomad4 AFR exome

AF:

0.000958

Gnomad4 AMR exome

AF:

0.00292

Gnomad4 ASJ exome

AF:

0.00621

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.00321

Gnomad4 FIN exome

AF:

0.00188

Gnomad4 NFE exome

AF:

0.00610

Gnomad4 OTH exome

AF:

0.00507

GnomAD4 genome

AF:

0.00362

AC:

551

AN:

152296

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

263

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00532

Gnomad4 OTH

AF:

0.00426

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Carpenter syndrome

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 07, 2023

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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