Genetic Variant NM_001286060.2:c.592A>C (chr11-82982185-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001286060.2(RAB30):c.592A>C(p.Thr198Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T198S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RAB30
NM_001286060.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.24

Publications

0 publications found

Variant links:

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]

RAB30 links:

ENSG00000254698 (HGNC:):

ENSG00000254698 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29383856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286060.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB30	NM_001286060.2	MANE Select	c.592A>C	p.Thr198Pro	missense	Exon 5 of 5	NP_001272989.1	Q15771-1
RAB30	NM_001286059.2		c.592A>C	p.Thr198Pro	missense	Exon 5 of 5	NP_001272988.1	Q15771-1
RAB30	NM_001286061.1		c.592A>C	p.Thr198Pro	missense	Exon 5 of 5	NP_001272990.1	A8K5R1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB30	ENST00000527633.6	TSL:1 MANE Select	c.592A>C	p.Thr198Pro	missense	Exon 5 of 5	ENSP00000435089.1	Q15771-1
RAB30	ENST00000533486.5	TSL:1	c.592A>C	p.Thr198Pro	missense	Exon 6 of 6	ENSP00000435189.1	Q15771-1
RAB30	ENST00000534141.5	TSL:1	c.*93A>C		3_prime_UTR	Exon 5 of 5	ENSP00000434974.1	Q15771-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

0.0078

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

Eigen

Benign

-0.075

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.013

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

6.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.034

Sift4G

Benign

0.072

Polyphen

0.0050

Vest4

0.47

MutPred

0.43

Gain of disorder (P = 0.044)

MVP

0.50

MPC

1.0

ClinPred

0.61

GERP RS

6.0

Varity_R

0.25

gMVP

0.62

Mutation Taster

=72/28

polymorphism

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over