Genetic Variant RAB14:p.Ala85Ala (chr9-121190583-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016322.4(RAB14):c.255G>A(p.Ala85Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,612,616 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

RAB14
NM_016322.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.10

Publications

1 publications found

Variant links:

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

RAB14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 9-121190583-C-T is Benign according to our data. Variant chr9-121190583-C-T is described in ClinVar as Benign. ClinVar VariationId is 708724.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.1 with no splicing effect.

BS2

High AC in GnomAd4 at 258 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB14	NM_016322.4	MANE Select	c.255G>A	p.Ala85Ala	synonymous	Exon 4 of 8	NP_057406.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB14	ENST00000373840.9	TSL:1 MANE Select	c.255G>A	p.Ala85Ala	synonymous	Exon 4 of 8	ENSP00000362946.4	P61106
RAB14	ENST00000703999.1		c.255G>A	p.Ala85Ala	synonymous	Exon 4 of 8	ENSP00000515613.1	P61106
RAB14	ENST00000704000.1		c.255G>A	p.Ala85Ala	synonymous	Exon 4 of 8	ENSP00000515614.1	P61106

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

258

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00616

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00174

AC:

435

AN:

250616

AF XY:

0.00171

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00625

Gnomad NFE exome

AF:

0.00231

Gnomad OTH exome

AF:

0.00476

GnomAD4 exome

AF:

0.00187

AC:

2729

AN:

1460630

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1325

AN XY:

726600

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33394

American (AMR)

AF:

0.0000897

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00740

AC:

395

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00200

AC:

2218

AN:

1111276

Other (OTH)

AF:

0.00162

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

131

262

394

525

656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00170

AC:

258

AN:

151986

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41450

American (AMR)

AF:

0.000131

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00616

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00258

AC:

175

AN:

67956

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00223

Hom.:

Bravo

AF:

0.00114

EpiCase

AF:

0.00170

EpiControl

AF:

0.00172

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.5

(source)

DANN

Benign

0.74

PhyloP100

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over