chr16-2153359-C-T

Variant names:

• chr16-2153359-C-T
• rs780018086
• NM_014353.5:c.709C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014353.5(RAB26):​c.709C>T​(p.Arg237Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: RAB26 NM_014353.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• Publications: 1 publications found

Genes affected

RAB26 (HGNC:14259): (RAB26, member RAS oncogene family) Members of the RAB protein family, including RAB26, are important regulators of vesicular fusion and trafficking. The RAB family of small G proteins regulates intercellular vesicle trafficking, including exocytosis, endocytosis, and recycling (summary by Seki et al., 2000 [PubMed 11043516]).[supplied by OMIM, Nov 2010]

SNHG19 (HGNC:49574): (small nucleolar RNA host gene 19)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24514493).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014353.5. 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
	RAB26	NM_014353.5	MANE Select	c.709C>T	p.Arg237Cys	missense	Exon 9 of 9	NP_055168.2
	RAB26	NM_001308053.1		c.511C>T	p.Arg171Cys	missense	Exon 10 of 10	NP_001294982.1	Q9ULW5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB26	ENST00000210187.11	TSL:1 MANE Select	c.709C>T	p.Arg237Cys	missense	Exon 9 of 9	ENSP00000210187.6	Q9ULW5-1
	RAB26	ENST00000541451.5	TSL:1	c.511C>T	p.Arg171Cys	missense	Exon 10 of 10	ENSP00000441580.1	Q9ULW5-2
	RAB26	ENST00000564426.5	TSL:1	n.1142C>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250566 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461198 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 726892

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.7
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.12
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.026	D
Polyphen		0.99	D
Vest4		0.34
MutPred		0.35		Loss of MoRF binding (P = 0.0126)
MVP		0.66
MPC		0.43
ClinPred		1.0	D
GERP RS		2.3
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.44
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs780018086; hg19: chr16-2203360; COSMIC: COSV52954309; COSMIC: COSV52954309;