17-5346805-C-G

Variant names:

• chr17-5346805-C-G
• NM_004703.6:c.664C>G

Variant summary

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

The NM_004703.6(RABEP1):​c.664C>G​(p.His222Asp) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 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
RABEP1	NM_004703.6	c.664C>G	p.His222Asp	missense_variant	Exon 6 of 18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.664C>G	p.His222Asp	missense_variant	Exon 6 of 18	1	NM_004703.6	ENSP00000445408.2
RABEP1	ENST00000341923.10	c.664C>G	p.His222Asp	missense_variant	Exon 6 of 17	1		ENSP00000339569.6
RABEP1	ENST00000575475.2	n.700C>G		non_coding_transcript_exon_variant	Exon 5 of 14	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1420096 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704844

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: 0.00

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	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.7	.;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.010	.;D
Sift4G	Benign	0.49	T;T
Polyphen		1.0	D;D
Vest4		0.80
MutPred		0.13		Gain of disorder (P = 0.0948);Gain of disorder (P = 0.0948);
MVP		0.57
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.35

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: chr17-5250100;