3-19978382-A-G

Position:

• chr3-19978382-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004162.5(RAB5A):​c.511A>G​(p.Asn171Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB5A NM_004162.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.22

Genes affected

RAB5A (HGNC:9783): (RAB5A, member RAS oncogene family) Enables GDP binding activity; GTP binding activity; and GTPase activity. Involved in several processes, including amyloid-beta clearance by transcytosis; early endosome to late endosome transport; and regulation of exocytosis. Located in several cellular components, including cytoplasmic side of early endosome membrane; nucleoplasm; and terminal bouton. [provided by Alliance of Genome Resources, Apr 2022]

RAB5A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB5A	NM_004162.5	c.511A>G	p.Asn171Asp	missense_variant	5/6	ENST00000273047.9	NP_004153.2
RAB5A	NM_001292048.2	c.469A>G	p.Asn157Asp	missense_variant	5/6		NP_001278977.1
RAB5A	XM_047448648.1	c.250A>G	p.Asn84Asp	missense_variant	5/6		XP_047304604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB5A	ENST00000273047.9	c.511A>G	p.Asn171Asp	missense_variant	5/6	1	NM_004162.5	ENSP00000273047.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.511A>G (p.N171D) alteration is located in exon 5 (coding exon 4) of the RAB5A gene. This alteration results from a A to G substitution at nucleotide position 511, causing the asparagine (N) at amino acid position 171 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;.
Eigen	Benign	-0.056
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-0.010	N;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.026	D;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0050	B;.
Vest4		0.77
MutPred		0.45		Loss of MoRF binding (P = 0.0751);.;
MVP		0.79
MPC		0.57
ClinPred		0.92	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.61

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-20019874;