16-2148865-C-A

Variant names:

• chr16-2148865-C-A
• rs771023224
• NM_014353.5:c.82C>A

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.82C>A​(p.Pro28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000799 in 1,250,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P28S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: RAB26 NM_014353.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963
• Publications: 0 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]

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=0.11616248).

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.82C>A	p.Pro28Thr	missense	Exon 1 of 9	NP_055168.2
	RAB26	NM_001308053.1		c.-117C>A		5_prime_UTR	Exon 2 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.82C>A	p.Pro28Thr	missense	Exon 1 of 9	ENSP00000210187.6	Q9ULW5-1
	RAB26	ENST00000541451.5	TSL:1	c.-117C>A		5_prime_UTR	Exon 2 of 10	ENSP00000441580.1	Q9ULW5-2
	RAB26	ENST00000564426.5	TSL:1	n.126C>A		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.99e-7 AC: 1 AN: 1250812 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 614084

African (AFR) AF: 0.00 AC: 0 AN: 25300

American (AMR) AF: 0.00 AC: 0 AN: 18954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20604

East Asian (EAS) AF: 0.00 AC: 0 AN: 27696

South Asian (SAS) AF: 0.00 AC: 0 AN: 59238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4572

European-Non Finnish (NFE) AF: 9.91e-7 AC: 1 AN: 1008634

Other (OTH) AF: 0.00 AC: 0 AN: 50800

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.4
DANN	Benign	0.62
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.96
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.0070
Sift	Uncertain	0.027	D
Sift4G	Benign	0.29	T
Polyphen		0.0080	B
Vest4		0.15
MutPred		0.19		Loss of loop (P = 0.0112)
MVP		0.27
MPC		0.25
ClinPred		0.044	T
GERP RS		2.0
PromoterAI		-0.070	Neutral
Varity_R		0.054
gMVP		0.39
Mutation Taster		=98/2	polymorphism

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: rs771023224; hg19: chr16-2198866;