Variant 22-23160959-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004914.5(RAB36):c.700A>G(p.Ser234Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Consequence

RAB36
NM_004914.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.152

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:

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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=0.06327745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB36	NM_004914.5 linkuse as main transcript	c.700A>G	p.Ser234Gly	missense_variant	10/11	ENST00000263116.8	NP_004905.3	O95755

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB36	ENST00000263116.8 linkuse as main transcript	c.700A>G	p.Ser234Gly	missense_variant	10/11	1	NM_004914.5	ENSP00000263116.3		O95755
RAB36	ENST00000341989.9 linkuse as main transcript	c.634A>G	p.Ser212Gly	missense_variant	9/10	1		ENSP00000343494.5		O95755

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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 08, 2024

The c.898A>G (p.S300G) alteration is located in exon 10 (coding exon 10) of the RAB36 gene. This alteration results from a A to G substitution at nucleotide position 898, causing the serine (S) at amino acid position 300 to be replaced by a glycine (G). 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

0.059

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.8

DANN

Benign

0.91

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.025

Sift

Benign

0.52

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0

B;B

Vest4

0.086

MutPred

0.29

Loss of phosphorylation at S300 (P = 0.018);.;

MVP

0.75

MPC

0.37

ClinPred

0.077

GERP RS

3.4

Varity_R

0.035

gMVP

0.17

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