12-71785594-C-A

Variant names:

• chr12-71785594-C-A
• NM_014999.4:c.599C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014999.4(RAB21):​c.599C>A​(p.Thr200Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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)
• Consequence: RAB21 NM_014999.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

Genes affected

RAB21 (HGNC:18263): (RAB21, member RAS oncogene family) This gene belongs to the Rab family of monomeric GTPases, which are involved in the control of cellular membrane traffic. The encoded protein plays a role in the targeted trafficking of integrins via its association with integrin alpha tails. As a consequence, the encoded protein is involved in the regulation of cell adhesion and migration. Expression of this gene is associated with a poor prognosis for glioma patients. This gene is downregulated by the tumor suppressor miR-200b, and miRNA-200b is itself downregulated in glioma tissues. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050245047).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014999.4. 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
	RAB21	NM_014999.4	MANE Select	c.599C>A	p.Thr200Asn	missense	Exon 7 of 7	NP_055814.1	Q9UL25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB21	ENST00000261263.5	TSL:1 MANE Select	c.599C>A	p.Thr200Asn	missense	Exon 7 of 7	ENSP00000261263.3	Q9UL25
	RAB21	ENST00000967018.1		c.614C>A	p.Thr205Asn	missense	Exon 7 of 7	ENSP00000637077.1
	RAB21	ENST00000358546.3	TSL:2	n.436C>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.089
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.050
Sift	Benign	0.35	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.19		Loss of phosphorylation at T200 (P = 0.0024)
MVP		0.28
MPC		0.41
ClinPred		0.16	T
GERP RS		3.6
Varity_R		0.050
gMVP		0.25
Mutation Taster		=92/8	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

hg19: chr12-72179374;