22-23145510-G-A

Position:

• chr22-23145510-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349877.1(RAB36):​c.145G>A​(p.Gly49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RAB36 NM_001349877.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.336

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]

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]

RAB36 (HGNC:):

ACMG classification

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=0.04025352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB36	NM_004914.5	c.-54G>A		5_prime_UTR_variant	1/11	ENST00000263116.8	NP_004905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB36	ENST00000263116.8	c.-54G>A		5_prime_UTR_variant	1/11	1	NM_004914.5	ENSP00000263116.3
RAB36	ENST00000341989.9	c.-54G>A		5_prime_UTR_variant	1/10	1		ENSP00000343494.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.145G>A (p.G49R) alteration is located in exon 1 (coding exon 1) of the RAB36 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the glycine (G) at amino acid position 49 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.24
DANN	Benign	0.84
DEOGEN2	Benign	0.0076	T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.027
Sift	Benign	0.99	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.0010	B;B
Vest4		0.080
MutPred		0.34		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.43
MPC		0.49
ClinPred		0.061	T
GERP RS		-8.6
Varity_R		0.047
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-23487697;