9-121186097-T-C

Variant names:

• chr9-121186097-T-C
• rs10760153
• NM_016322.4:c.351+856A>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.351+856A>G 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 151,958 control chromosomes in the GnomAD database, including 12,061 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 (12061 hom., cov: 31)
• Consequence: RAB14 NM_016322.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB14	NM_016322.4	c.351+856A>G		intron_variant	Intron 5 of 7	ENST00000373840.9	NP_057406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB14	ENST00000373840.9	c.351+856A>G		intron_variant	Intron 5 of 7	1	NM_016322.4	ENSP00000362946.4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54271 AN: 151840 Hom.: 12049 Cov.: 31

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.427

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: 54282 AN: 151958 Hom.: 12061 Cov.: 31 AF XY: 0.367 AC XY: 27277 AN XY: 74240

African (AFR) AF: 0.0837 AC: 3475 AN: 41504

American (AMR) AF: 0.484 AC: 7373 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3468

East Asian (EAS) AF: 0.557 AC: 2865 AN: 5146

South Asian (SAS) AF: 0.644 AC: 3101 AN: 4812

European-Finnish (FIN) AF: 0.487 AC: 5128 AN: 10536

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29020 AN: 67930

Other (OTH) AF: 0.404 AC: 854 AN: 2112

Alfa AF: 0.400 Hom.: 5709

Bravo AF: 0.344

Asia WGS AF: 0.537 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		-0.12
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: rs10760153; hg19: chr9-123948375; COSMIC: COSV65788187;