1-202881084-A-G

Position:

• chr1-202881084-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000367262.4(RABIF):​c.266T>C​(p.Ile89Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RABIF ENST00000367262.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.87

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35125244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABIF	NM_002871.5	c.266T>C	p.Ile89Thr	missense_variant	2/2	ENST00000367262.4	NP_002862.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABIF	ENST00000367262.4	c.266T>C	p.Ile89Thr	missense_variant	2/2	1	NM_002871.5	ENSP00000356231.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

The c.266T>C (p.I89T) alteration is located in exon 2 (coding exon 2) of the RABIF gene. This alteration results from a T to C substitution at nucleotide position 266, causing the isoleucine (I) at amino acid position 89 to be replaced by a threonine (T). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.25
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.59	P
Vest4		0.30
MutPred		0.45		Loss of sheet (P = 0.0457);
MVP		0.60
MPC		0.27
ClinPred		0.71	D
GERP RS		5.8
Varity_R		0.24
gMVP		0.70

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: chr1-202850212;