9-121178807-A-G

Position:

• chr9-121178807-A-G

Variant summary

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

The NM_016322.4(RAB14):​c.*2589T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,126 control chromosomes in the GnomAD database, including 35,614 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 0.68 (35613 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: RAB14 NM_016322.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB14	NM_016322.4	c.*2589T>C		3_prime_UTR_variant	8/8	ENST00000373840.9	NP_057406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB14	ENST00000373840	c.*2589T>C		3_prime_UTR_variant	8/8	1	NM_016322.4	ENSP00000362946.4

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102886 AN: 152006 Hom.: 35576 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.677 AC: 102978 AN: 152124 Hom.: 35613 Cov.: 33 AF XY: 0.682 AC XY: 50709 AN XY: 74350

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.703

Alfa AF: 0.686 Hom.: 14872

Bravo AF: 0.679

Asia WGS AF: 0.890 AC: 3094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.77

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: rs2057469; hg19: chr9-123941085;