9-121178807-A-G

Variant names:

• chr9-121178807-A-G
• rs2057469
• NM_016322.4:c.*2589T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016322.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB14	NM_016322.4	MANE Select	c.*2589T>C		3_prime_UTR	Exon 8 of 8	NP_057406.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB14	ENST00000373840.9	TSL:1 MANE Select	c.*2589T>C		3_prime_UTR	Exon 8 of 8	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.552 AC: 22900 AN: 41494

American (AMR) AF: 0.767 AC: 11726 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3470

East Asian (EAS) AF: 0.957 AC: 4965 AN: 5188

South Asian (SAS) AF: 0.919 AC: 4435 AN: 4824

European-Finnish (FIN) AF: 0.657 AC: 6936 AN: 10556

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47103 AN: 67978

Other (OTH) AF: 0.703 AC: 1486 AN: 2114

Alfa AF: 0.689 Hom.: 25069

Bravo AF: 0.679

Asia WGS AF: 0.890 AC: 3094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.77
PhyloP100		0.22
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: rs2057469; hg19: chr9-123941085;