Genetic Variant NM_001365613.2:c.3913C>A (chr20-17615964-G-T) – 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_001365613.2(RRBP1):c.3913C>A(p.Gln1305Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RRBP1
NM_001365613.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

0 publications found

Variant links:

Genes affected

RRBP1 (HGNC:10448): (ribosome binding protein 1) This gene encodes a ribosome-binding protein of the endoplasmic reticulum (ER) membrane. Studies suggest that this gene plays a role in ER proliferation, secretory pathways and secretory cell differentiation, and mediation of ER-microtubule interactions. Alternative splicing has been observed and protein isoforms are characterized by regions of N-terminal decapeptide and C-terminal heptad repeats. Splicing of the tandem repeats results in variations in ribosome-binding affinity and secretory function. The full-length nature of variants which differ in repeat length has not been determined. Pseudogenes of this gene have been identified on chromosomes 3 and 7, and RRBP1 has been excluded as a candidate gene in the cause of Alagille syndrome, the result of a mutation in a nearby gene on chromosome 20p12. [provided by RefSeq, Apr 2012]

RRBP1 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=0.194338).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365613.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RRBP1	NM_001365613.2	MANE Select	c.3913C>A	p.Gln1305Lys	missense	Exon 22 of 25	NP_001352542.1	Q9P2E9-1
RRBP1	NM_001042576.2		c.2614C>A	p.Gln872Lys	missense	Exon 23 of 26	NP_001036041.2	Q9P2E9-3
RRBP1	NM_004587.3		c.2614C>A	p.Gln872Lys	missense	Exon 22 of 25	NP_004578.3	Q9P2E9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RRBP1	ENST00000377813.6	TSL:1 MANE Select	c.3913C>A	p.Gln1305Lys	missense	Exon 22 of 25	ENSP00000367044.1	Q9P2E9-1
RRBP1	ENST00000246043.8	TSL:1	c.3913C>A	p.Gln1305Lys	missense	Exon 20 of 23	ENSP00000246043.4	Q9P2E9-1
RRBP1	ENST00000360807.8	TSL:1	c.2614C>A	p.Gln872Lys	missense	Exon 22 of 25	ENSP00000354045.4	Q9P2E9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457370

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725160

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111904

Other (OTH)

AF:

0.00

AC:

AN:

60362

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

M_CAP

Benign

0.0085

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

PhyloP100

4.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

REVEL

Benign

0.067

Sift

Benign

0.070

Sift4G

Benign

0.83

Polyphen

0.89

Vest4

0.37

MutPred

0.15

Gain of ubiquitination at Q1305 (P = 0.0018)

MVP

0.56

MPC

0.16

ClinPred

0.82

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.18

Mutation Taster

=79/21

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over