chr17-5381394-C-A

Variant names:

• chr17-5381394-C-A
• rs117554009
• NM_004703.6:c.2376C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_004703.6(RABEP1):​c.2376C>A​(p.Thr792Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,609,600 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. T792T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00038 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (3 hom.)
• Consequence: RABEP1 NM_004703.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 4 publications found

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]

NUP88 Gene-Disease associations (from GenCC):

• fetal akinesia deformation sequence 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004703.6. 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
	RABEP1	NM_004703.6	MANE Select	c.2376C>A	p.Thr792Thr	synonymous	Exon 17 of 18	NP_004694.2
	RABEP1	NM_001083585.3		c.2277C>A	p.Thr759Thr	synonymous	Exon 16 of 17	NP_001077054.1	Q15276-2
	RABEP1	NM_001291581.2		c.2247C>A	p.Thr749Thr	synonymous	Exon 16 of 17	NP_001278510.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP1	ENST00000537505.6	TSL:1 MANE Select	c.2376C>A	p.Thr792Thr	synonymous	Exon 17 of 18	ENSP00000445408.2	Q15276-1
	RABEP1	ENST00000341923.10	TSL:1	c.2277C>A	p.Thr759Thr	synonymous	Exon 16 of 17	ENSP00000339569.6	Q15276-2
	NUP88	ENST00000573169.1	TSL:1	n.71+4744G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152116 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00962

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00109 AC: 268 AN: 245116 AF XY: 0.000850

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000337

GnomAD4 exome AF: 0.000319 AC: 465 AN: 1457366 Hom.: 3 Cov.: 29 AF XY: 0.000306 AC XY: 222 AN XY: 724736

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.0000229 AC: 1 AN: 43728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.0106 AC: 420 AN: 39570

South Asian (SAS) AF: 0.000177 AC: 15 AN: 84924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110672

Other (OTH) AF: 0.000399 AC: 24 AN: 60208

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152234 Hom.: 1 Cov.: 33 AF XY: 0.000457 AC XY: 34 AN XY: 74420

African (AFR) AF: 0.0000241 AC: 1 AN: 41540

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00964 AC: 50 AN: 5186

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.0000274 Hom.: 0

Bravo AF: 0.000710

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.80
DANN	Benign	0.80
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs117554009; hg19: chr17-5284689;