Genetic Variant RABAC1:p.Arg32Leu (chr19-41958910-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006423.3(RABAC1):c.95G>T(p.Arg32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R32Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RABAC1
NM_006423.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

Publications

0 publications found

Variant links:

Genes affected

RABAC1 (HGNC:9794): (Rab acceptor 1) Enables identical protein binding activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RABAC1 links:

ENSG00000285505 (HGNC:):

ENSG00000285505 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26152933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006423.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABAC1	NM_006423.3	MANE Select	c.95G>T	p.Arg32Leu	missense	Exon 2 of 5	NP_006414.2	Q9UI14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RABAC1	ENST00000222008.11	TSL:1 MANE Select	c.95G>T	p.Arg32Leu	missense	Exon 2 of 5	ENSP00000222008.5	Q9UI14
ENSG00000285505	ENST00000644613.1		n.*19G>T		non_coding_transcript_exon	Exon 23 of 25	ENSP00000494711.1	A0A2R8YEY8
ENSG00000285505	ENST00000644613.1		n.*19G>T		3_prime_UTR	Exon 23 of 25	ENSP00000494711.1	A0A2R8YEY8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1440312

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715866

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33228

American (AMR)

AF:

0.00

AC:

AN:

42310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25798

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38964

South Asian (SAS)

AF:

0.00

AC:

AN:

84646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105638

Other (OTH)

AF:

0.00

AC:

AN:

59714

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

Eigen

Benign

-0.11

Eigen_PC

Benign

0.045

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.84

M_CAP

Benign

0.018

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

2.2

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.10

Sift

Uncertain

0.019

Sift4G

Uncertain

0.021

Polyphen

0.22

Vest4

0.58

MutPred

0.36

Loss of MoRF binding (P = 0.0089)

MVP

0.64

MPC

0.83

ClinPred

0.98

GERP RS

4.3

PromoterAI

-0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.60

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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