6-57188721-G-A

Variant names:

• chr6-57188721-G-A
• rs9382689
• NM_016277.5:c.*1740C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016277.5(RAB23):​c.*1740C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,918 control chromosomes in the GnomAD database, including 5,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5488 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RAB23 NM_016277.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.213
• Publications: 3 publications found

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]

BAG2 (HGNC:938): (BAG cochaperone 2) BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The predicted BAG2 protein contains 211 amino acids. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-57188721-G-A is Benign according to our data. Variant chr6-57188721-G-A is described in ClinVar as Benign. ClinVar VariationId is 910337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016277.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB23	NM_016277.5	MANE Select	c.*1740C>T		3_prime_UTR	Exon 7 of 7	NP_057361.3
	BAG2	NM_004282.4	MANE Select	c.*4531G>A		3_prime_UTR	Exon 3 of 3	NP_004273.1	O95816-1
	RAB23	NM_001278666.2		c.*1740C>T		3_prime_UTR	Exon 7 of 7	NP_001265595.1	Q9ULC3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB23	ENST00000468148.6	TSL:1 MANE Select	c.*1740C>T		3_prime_UTR	Exon 7 of 7	ENSP00000417610.1	Q9ULC3
	BAG2	ENST00000370693.5	TSL:1 MANE Select	c.*4531G>A		3_prime_UTR	Exon 3 of 3	ENSP00000359727.4	O95816-1
	RAB23	ENST00000875526.1		c.*1740C>T		3_prime_UTR	Exon 7 of 7	ENSP00000545585.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39418 AN: 151800 Hom.: 5476 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.243

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.260 AC: 39474 AN: 151918 Hom.: 5488 Cov.: 32 AF XY: 0.260 AC XY: 19282 AN XY: 74234

African (AFR) AF: 0.346 AC: 14316 AN: 41410

American (AMR) AF: 0.199 AC: 3044 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3466

East Asian (EAS) AF: 0.139 AC: 716 AN: 5166

South Asian (SAS) AF: 0.127 AC: 610 AN: 4816

European-Finnish (FIN) AF: 0.353 AC: 3720 AN: 10532

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15422 AN: 67938

Other (OTH) AF: 0.241 AC: 509 AN: 2112

Alfa AF: 0.252 Hom.: 731

Bravo AF: 0.255

Asia WGS AF: 0.155 AC: 536 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	RAB23-related Carpenter syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9382689; hg19: chr6-57053519;