NM_016322.4:c.284+915A>G

Variant names:

• chr9-121189639-T-C
• rs9408928
• NM_016322.4:c.284+915A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016322.4(RAB14):​c.284+915A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,180 control chromosomes in the GnomAD database, including 169 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 0.043 (169 hom., cov: 32)
• Consequence: RAB14 NM_016322.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 14 publications found

Genes affected

RAB14 (HGNC:16524): (RAB14, member RAS oncogene family) RAB14 belongs to the large RAB family of low molecular mass GTPases that are involved in intracellular membrane trafficking. These proteins act as molecular switches that flip between an inactive GDP-bound state and an active GTP-bound state in which they recruit downstream effector proteins onto membranes (Junutula et al., 2004 [PubMed 15004230]).[supplied by OMIM, Mar 2009]

RAB14 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB14	NM_016322.4	c.284+915A>G		intron_variant	Intron 4 of 7	ENST00000373840.9	NP_057406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB14	ENST00000373840.9	c.284+915A>G		intron_variant	Intron 4 of 7	1	NM_016322.4	ENSP00000362946.4

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6513 AN: 152062 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0428 AC: 6515 AN: 152180 Hom.: 169 Cov.: 32 AF XY: 0.0408 AC XY: 3035 AN XY: 74400

African (AFR) AF: 0.0242 AC: 1006 AN: 41542

American (AMR) AF: 0.0256 AC: 391 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3466

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5190

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4828

European-Finnish (FIN) AF: 0.0644 AC: 683 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4137 AN: 67970

Other (OTH) AF: 0.0398 AC: 84 AN: 2108

Alfa AF: 0.0539 Hom.: 771

Bravo AF: 0.0405

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.87
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs9408928; hg19: chr9-123951917;