16-2152863-C-A

Variant names:

• chr16-2152863-C-A
• rs573136070
• NM_014353.5:c.512C>A

Variant summary

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

The NM_014353.5(RAB26):​c.512C>A​(p.Ala171Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A171V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB26 NM_014353.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.512C>A	p.Ala171Glu	missense	Exon 6 of 9	NP_055168.2
	RAB26	NM_001308053.1		c.314C>A	p.Ala105Glu	missense	Exon 7 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.512C>A	p.Ala171Glu	missense	Exon 6 of 9	ENSP00000210187.6	Q9ULW5-1
	RAB26	ENST00000541451.5	TSL:1	c.314C>A	p.Ala105Glu	missense	Exon 7 of 10	ENSP00000441580.1	Q9ULW5-2
	RAB26	ENST00000564426.5	TSL:1	n.742C>A		non_coding_transcript_exon	Exon 8 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 244996 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.80
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.33	N
PhyloP100		5.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.38
Sift	Benign	0.83	T
Sift4G	Benign	1.0	T
Polyphen		0.12	B
Vest4		0.63
MutPred		0.44		Loss of sheet (P = 0.0817)
MVP		0.51
MPC		0.51
ClinPred		0.44	T
GERP RS		2.9
PromoterAI		-0.025	Neutral
Varity_R		0.42
gMVP		0.80

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: rs573136070; hg19: chr16-2202864;