1-202889022-C-G

Variant names:

• chr1-202889022-C-G
• NM_002871.5:c.77G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PP3_Strong

The NM_002871.5(RABIF):​c.77G>C​(p.Cys26Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RABIF NM_002871.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69

Genes affected

RABIF (HGNC:9797): (RAB interacting factor) This gene encodes a member of the SCE4/YPT1/RAB family of small GTP-binding proteins that are involved in the regulation of intracellular vesicular transport. This protein stimulates GTP-GDP exchange in SEC4, and to a lesser extent in YPT1 and RAB3A, and may play a general role in vesicular transport. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity MSS4_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABIF	NM_002871.5	c.77G>C	p.Cys26Ser	missense_variant	Exon 1 of 2	ENST00000367262.4	NP_002862.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABIF	ENST00000367262.4	c.77G>C	p.Cys26Ser	missense_variant	Exon 1 of 2	1	NM_002871.5	ENSP00000356231.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77G>C (p.C26S) alteration is located in exon 1 (coding exon 1) of the RABIF gene. This alteration results from a G to C substitution at nucleotide position 77, causing the cysteine (C) at amino acid position 26 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-8.6	D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.75		Gain of phosphorylation at C26 (P = 0.0337);
MVP		0.56
MPC		0.77
ClinPred		1.0	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.96
gMVP		0.85

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: chr1-202858150;