Genetic Variant RAB14:p.Ala153Ala (chr9-121182941-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_016322.4(RAB14):c.459G>A(p.Ala153Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,606,444 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 9 hom. )

Consequence

RAB14
NM_016322.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.52

Publications

2 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 9-121182941-C-T is Benign according to our data. Variant chr9-121182941-C-T is described in ClinVar as Benign. ClinVar VariationId is 771735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.52 with no splicing effect.

BS2

High AC in GnomAd4 at 208 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.459G>A	p.Ala153Ala	synonymous	Exon 7 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.459G>A	p.Ala153Ala	synonymous	Exon 7 of 8	ENSP00000362946.4	P61106
RAB14	ENST00000703996.1		c.443G>A	p.Arg148Gln	missense	Exon 6 of 7	ENSP00000515610.1	A0A994J4B9
RAB14	ENST00000703999.1		c.459G>A	p.Ala153Ala	synonymous	Exon 7 of 8	ENSP00000515613.1	P61106

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000756

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00231

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00136

AC:

341

AN:

249936

AF XY:

0.00138

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.000995

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00210

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00201

AC:

2918

AN:

1454240

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

1397

AN XY:

722582

show subpopulations

African (AFR)

AF:

0.000540

AC:

AN:

33352

American (AMR)

AF:

0.000945

AC:

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

25958

East Asian (EAS)

AF:

0.00

AC:

AN:

39458

South Asian (SAS)

AF:

0.0000469

AC:

AN:

85308

European-Finnish (FIN)

AF:

0.00180

AC:

AN:

53228

Middle Eastern (MID)

AF:

0.00317

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00236

AC:

2617

AN:

1106746

Other (OTH)

AF:

0.00155

AC:

AN:

60066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

141

282

422

563

704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.00137

AC:

208

AN:

152204

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41532

American (AMR)

AF:

0.000392

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000756

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00231

AC:

157

AN:

68016

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00224

Hom.:

Bravo

AF:

0.00138

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.3

(source)

DANN

Benign

0.64

PhyloP100

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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