NM_016277.5:c.529A>G

Variant names:

• chr6-57193887-T-C
• NM_016277.5:c.529A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016277.5(RAB23):​c.529A>G​(p.Ile177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAB23 NM_016277.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059957653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB23	NM_016277.5	c.529A>G	p.Ile177Val	missense_variant	Exon 6 of 7	ENST00000468148.6	NP_057361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB23	ENST00000468148.6	c.529A>G	p.Ile177Val	missense_variant	Exon 6 of 7	1	NM_016277.5	ENSP00000417610.1
RAB23	ENST00000317483.4	c.529A>G	p.Ile177Val	missense_variant	Exon 6 of 7	1		ENSP00000320413.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460762 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.6
DANN	Benign	0.76
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.62	T;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.063
Sift	Benign	0.54	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0	B;B
Vest4		0.075
MutPred		0.21		Gain of ubiquitination at K174 (P = 0.1047);Gain of ubiquitination at K174 (P = 0.1047);
MVP		0.49
MPC		0.15
ClinPred		0.038	T
GERP RS		0.71
Varity_R		0.013
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-57058685;