rs779964235

Variant names:

• chr17-5338059-C-A
• NM_004703.6:c.569C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-5338059-C-A
• chr17-5338059-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004703.6(RABEP1):​c.569C>A​(p.Pro190Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RABEP1 NM_004703.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP1	NM_004703.6	c.569C>A	p.Pro190Gln	missense_variant	Exon 5 of 18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.569C>A	p.Pro190Gln	missense_variant	Exon 5 of 18	1	NM_004703.6	ENSP00000445408.2
RABEP1	ENST00000341923.10	c.569C>A	p.Pro190Gln	missense_variant	Exon 5 of 17	1		ENSP00000339569.6
RABEP1	ENST00000575475.2	n.605C>A		non_coding_transcript_exon_variant	Exon 4 of 14	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461250 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726932

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.2	.;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	.;D
Sift4G	Benign	0.20	T;T
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.60		Gain of MoRF binding (P = 0.0237);Gain of MoRF binding (P = 0.0237);
MVP		0.52
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.65
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-5241354;