NM_014999.4:c.400A>T

Variant names:

• chr12-71782039-A-T
• NM_014999.4:c.400A>T

Variant summary

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

The NM_014999.4(RAB21):​c.400A>T​(p.Ile134Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RAB21 NM_014999.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56
• 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: 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_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.400A>T	p.Ile134Leu	missense	Exon 5 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.400A>T	p.Ile134Leu	missense	Exon 5 of 7	ENSP00000261263.3	Q9UL25
	RAB21	ENST00000967018.1		c.415A>T	p.Ile139Leu	missense	Exon 5 of 7	ENSP00000637077.1
	RAB21	ENST00000358546.3	TSL:2	n.237A>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	0.24
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.063
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.27	N
PhyloP100		4.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.25
Sift	Benign	0.17	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.47
MutPred		0.57		Gain of catalytic residue at I134 (P = 0.0435)
MVP		0.60
MPC		0.37
ClinPred		0.75	D
GERP RS		4.4
Varity_R		0.51
gMVP		0.44
Mutation Taster		=64/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-72175819;