chr6-57187131-T-C

Variant names:

• chr6-57187131-T-C
• rs72868608
• NM_016277.5:c.*3330A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_016277.5(RAB23):​c.*3330A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,172 control chromosomes in the GnomAD database, including 1,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1637 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: 0.770
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 6-57187131-T-C is Benign according to our data. Variant chr6-57187131-T-C is described in ClinVar as Benign. ClinVar VariationId is 908519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 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.*3330A>G		3_prime_UTR	Exon 7 of 7	NP_057361.3
	BAG2	NM_004282.4	MANE Select	c.*2941T>C		3_prime_UTR	Exon 3 of 3	NP_004273.1	O95816-1
	RAB23	NM_001278666.2		c.*3330A>G		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.*3330A>G		3_prime_UTR	Exon 7 of 7	ENSP00000417610.1	Q9ULC3
	BAG2	ENST00000370693.5	TSL:1 MANE Select	c.*2941T>C		3_prime_UTR	Exon 3 of 3	ENSP00000359727.4	O95816-1
	RAB23	ENST00000875526.1		c.*3330A>G		3_prime_UTR	Exon 7 of 7	ENSP00000545585.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21740 AN: 152054 Hom.: 1632 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.150

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: 0.143 AC: 21759 AN: 152172 Hom.: 1637 Cov.: 32 AF XY: 0.142 AC XY: 10564 AN XY: 74386

African (AFR) AF: 0.157 AC: 6502 AN: 41520

American (AMR) AF: 0.112 AC: 1713 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3470

East Asian (EAS) AF: 0.0433 AC: 225 AN: 5192

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1899 AN: 10564

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9915 AN: 67984

Other (OTH) AF: 0.148 AC: 313 AN: 2116

Alfa AF: 0.147 Hom.: 218

Bravo AF: 0.142

Asia WGS AF: 0.0440 AC: 153 AN: 3454

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	-0.21
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.77
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: rs72868608; hg19: chr6-57051929;