chr19-11325497-C-T

Variant names:

• chr19-11325497-C-T
• NM_004283.4:c.561G>A

Variant summary

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

The NM_004283.4(RAB3D):​c.561G>A​(p.Met187Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB3D NM_004283.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

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]

TSPAN16 (HGNC:30725): (tetraspanin 16) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein might couple to signal transduction pathways and possibly modulate cellular activation and adhesion in haemopoietic and neural tissue. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

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_004283.4. 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
	RAB3D	NM_004283.4	MANE Select	c.561G>A	p.Met187Ile	missense	Exon 5 of 5	NP_004274.1	A0A024R7G2
	TSPAN16	NM_012466.4		c.688-1297C>T		intron	N/A	NP_036598.1	Q9UKR8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3D	ENST00000222120.8	TSL:1 MANE Select	c.561G>A	p.Met187Ile	missense	Exon 5 of 5	ENSP00000222120.2	O95716
	TSPAN16	ENST00000316737.5	TSL:1	c.688-1297C>T		intron	N/A	ENSP00000319486.1	Q9UKR8-1
	RAB3D	ENST00000903414.1		c.597G>A	p.Met199Ile	missense	Exon 5 of 5	ENSP00000573473.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

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	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	-0.0021	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.54
Sift	Benign	0.072	T
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.43		Gain of methylation at K186 (P = 0.0279)
MVP		0.89
MPC		0.46
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.52
gMVP		0.64
Mutation Taster		=11/89	disease causing

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: chr19-11436173;