rs201050515

Variant names:

• chr17-5380401-A-G
• rs201050515
• NM_004703.6:c.2309A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-5380401-A-G
• chr17-5380401-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004703.6(RABEP1):​c.2309A>G​(p.Glu770Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,421,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RABEP1 NM_004703.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.27

Genes affected

RABEP1 (HGNC:17677): (rabaptin, RAB GTPase binding effector protein 1) Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in endocytic vesicle and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

NUP88 (HGNC:8067): (nucleoporin 88) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3232413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP1	NM_004703.6	c.2309A>G	p.Glu770Gly	missense_variant	Exon 16 of 18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.2309A>G	p.Glu770Gly	missense_variant	Exon 16 of 18	1	NM_004703.6	ENSP00000445408.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1421910 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 703400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000259

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.40	T
REVEL	Benign	0.098
Sift4G	Uncertain	0.057	T
Polyphen		0.80	P
Vest4		0.37
MutPred		0.41		Gain of MoRF binding (P = 0.071);
MVP		0.22
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.13

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: rs201050515; hg19: chr17-5283696;