19-11337346-G-C

Position:

• chr19-11337346-G-C

Variant summary

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

The NM_004283.4(RAB3D):​c.54C>G​(p.Asn18Lys) variant causes a missense change involving the alteration of a non-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: 31)
• Consequence: RAB3D NM_004283.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

Genes affected

RAB3D (HGNC:9779): (RAB3D, member RAS oncogene family) Enables myosin V binding activity. Involved in bone resorption and positive regulation of regulated secretory pathway. Located in cytoplasmic microtubule and secretory vesicle. [provided by Alliance of Genome Resources, Apr 2022]

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
RAB3D	NM_004283.4	c.54C>G	p.Asn18Lys	missense_variant	2/5	ENST00000222120.8	NP_004274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB3D	ENST00000222120.8	c.54C>G	p.Asn18Lys	missense_variant	2/5	1	NM_004283.4	ENSP00000222120.2
RAB3D	ENST00000589655.1	c.54C>G	p.Asn18Lys	missense_variant	2/5	2		ENSP00000466000.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Oct 24, 2024

The c.54C>G (p.N18K) alteration is located in exon 2 (coding exon 1) of the RAB3D gene. This alteration results from a C to G substitution at nucleotide position 54, causing the asparagine (N) at amino acid position 18 to be replaced by a lysine (K). 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	Pathogenic	0.74
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;D
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.53	N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.9	D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.027	D;.
Sift4G	Benign	0.18	T;T
Polyphen		0.97	D;D
Vest4		0.74
MutPred		0.38		Gain of methylation at N18 (P = 0.0042);Gain of methylation at N18 (P = 0.0042);
MVP		0.84
MPC		0.66
ClinPred		0.93	D
GERP RS		3.3
Varity_R		0.60
gMVP		0.58

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: chr19-11448022;