chr22-23145499-C-A

Position:

chr22-23145499-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004914.5(RAB36):c.-65C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,606,996 control chromosomes in the GnomAD database, including 1 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 1 hom. )

Consequence

RAB36
NM_004914.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0750

Variant links:

Genes affected

RAB36 (HGNC:9775): (RAB36, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in protein transport. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB36 links:

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

RSPH14 links:

RAB36 (HGNC:):

RAB36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059880048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB36	NM_004914.5 linkuse as main transcript	c.-65C>A		5_prime_UTR_premature_start_codon_gain_variant	1/11	ENST00000263116.8	NP_004905.3	O95755
RAB36	NM_004914.5 linkuse as main transcript	c.-65C>A		5_prime_UTR_variant	1/11	ENST00000263116.8	NP_004905.3	O95755

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB36	ENST00000263116.8 linkuse as main transcript	c.-65C>A	5_prime_UTR_premature_start_codon_gain_variant	1/11	1	NM_004914.5	ENSP00000263116.3	O95755
RAB36	ENST00000341989.9 linkuse as main transcript	c.-65C>A	5_prime_UTR_premature_start_codon_gain_variant	1/10	1		ENSP00000343494.5	O95755
RAB36	ENST00000263116.8 linkuse as main transcript	c.-65C>A	5_prime_UTR_variant	1/11	1	NM_004914.5	ENSP00000263116.3	O95755
RAB36	ENST00000341989.9 linkuse as main transcript	c.-65C>A	5_prime_UTR_variant	1/10	1		ENSP00000343494.5	O95755

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000454

AC:

AN:

242516

Hom.:

AF XY:

0.0000528

AC XY:

AN XY:

132648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000448

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1454724

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

723970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000413

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.134C>A (p.A45D) alteration is located in exon 1 (coding exon 1) of the RAB36 gene. This alteration results from a C to A substitution at nucleotide position 134, causing the alanine (A) at amino acid position 45 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.4

DANN

Benign

0.86

DEOGEN2

Benign

0.0087

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.43

B;P

Vest4

0.23

MutPred

0.29

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MVP

0.79

MPC

0.66

ClinPred

0.32

GERP RS

-0.71

Varity_R

0.18

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over