chr19-11333455-C-G

Position:

• chr19-11333455-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004283.4(RAB3D):​c.472+1992G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,948 control chromosomes in the GnomAD database, including 11,732 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11732 hom., cov: 31)
• Consequence: RAB3D NM_004283.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3D	NM_004283.4	c.472+1992G>C		intron_variant		ENST00000222120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3D	ENST00000222120.8	c.472+1992G>C		intron_variant		1	NM_004283.4	P1
RAB3D	ENST00000589655.1	c.472+1992G>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54186 AN: 151830 Hom.: 11726 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.403

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.357 AC: 54195 AN: 151948 Hom.: 11732 Cov.: 31 AF XY: 0.353 AC XY: 26222 AN XY: 74252

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.398

Alfa AF: 0.413 Hom.: 1790

Bravo AF: 0.345

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs896412; hg19: chr19-11444131;