11-82997264-G-C

Position:

• chr11-82997264-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001286060.2(RAB30):​c.53C>G​(p.Ala18Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB30 NM_001286060.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

RAB30 (HGNC:9770): (RAB30, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in Golgi organization. Located in Golgi cisterna; cis-Golgi network; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB30	NM_001286060.2	c.53C>G	p.Ala18Gly	missense_variant	2/5	ENST00000527633.6	NP_001272989.1
RAB30	NM_001286059.2	c.53C>G	p.Ala18Gly	missense_variant	2/5		NP_001272988.1
RAB30	NM_001286061.1	c.53C>G	p.Ala18Gly	missense_variant	2/5		NP_001272990.1
RAB30	NM_014488.5	c.53C>G	p.Ala18Gly	missense_variant	3/6		NP_055303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB30	ENST00000527633.6	c.53C>G	p.Ala18Gly	missense_variant	2/5	1	NM_001286060.2	ENSP00000435089	P1
	ENST00000527550.1	n.373-33523C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 07, 2021

The c.53C>G (p.A18G) alteration is located in exon 3 (coding exon 1) of the RAB30 gene. This alteration results from a C to G substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 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	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;D;.;D;D;T;T;T;T;T;T;T;D;.
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;.;D;.;.;D;D;T;D;D;D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	-0.085	N;N;N;N;N;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.1	.;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.011	.;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;.;.;D;D;D;D;.;D;.
Polyphen		0.99	D;D;.;D;D;.;.;P;.;.;.;.;.;.
Vest4		0.61
MutPred		0.51		Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);Gain of methylation at K22 (P = 0.1442);
MVP		0.74
MPC		1.9
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.66
gMVP		0.82

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: chr11-82708306;