20-17614835-C-G

Variant names:

• chr20-17614835-C-G
• rs551007819
• NM_001365613.2:c.4096G>C

Variant summary

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

The NM_001365613.2(RRBP1):​c.4096G>C​(p.Ala1366Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RRBP1 NM_001365613.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28

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]

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 rank	MANE	Protein	UniProt
RRBP1	NM_001365613.2	c.4096G>C	p.Ala1366Pro	missense_variant	Exon 24 of 25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2	c.2797G>C	p.Ala933Pro	missense_variant	Exon 25 of 26		NP_001036041.2
RRBP1	NM_004587.3	c.2797G>C	p.Ala933Pro	missense_variant	Exon 24 of 25		NP_004578.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6	c.4096G>C	p.Ala1366Pro	missense_variant	Exon 24 of 25	1	NM_001365613.2	ENSP00000367044.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;.;T;T;.;.;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D;.;D;.;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	.;.;M;M;.;.;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.9	.;.;D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	.;.;D;D;D;D;D
Sift4G	Benign	0.15	T;T;D;D;T;T;T
Polyphen		1.0, 1.0	.;.;D;D;D;D;.
Vest4		0.66
MutPred		0.11		.;.;Loss of MoRF binding (P = 0.0849);Loss of MoRF binding (P = 0.0849);.;.;.;
MVP		0.53
MPC		0.53
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.26
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs551007819; hg19: chr20-17595480;