NM_004703.6:c.5C>T

Variant names:

• chr17-5282491-C-T
• NM_004703.6:c.5C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_004703.6(RABEP1):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,149,114 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: 30)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: RABEP1 NM_004703.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535

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 3 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity RABE1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP1	NM_004703.6	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 18	1	NM_004703.6	ENSP00000445408.2
RABEP1	ENST00000341923.10	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 17	1		ENSP00000339569.6
RABEP1	ENST00000575475.2	n.170C>T		non_coding_transcript_exon_variant	Exon 1 of 14	1
RABEP1	ENST00000575991.1	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 3	4		ENSP00000459550.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1149114 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 556706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000713

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0089	T;T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.26	T;T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.93	.;N;N
REVEL	Benign	0.078
Sift	Pathogenic	0.0	.;D;T
Sift4G	Uncertain	0.031	.;D;D
Polyphen		0.72, 0.82	.;P;P
Vest4		0.29, 0.25
MutPred		0.16		Gain of solvent accessibility (P = 0.1154);Gain of solvent accessibility (P = 0.1154);Gain of solvent accessibility (P = 0.1154);
MVP		0.43
ClinPred		0.79	D
GERP RS		2.4
Varity_R		0.11
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-5185786;