2-73088083-A-C

Position:

• chr2-73088083-A-C

Variant summary

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

The NM_001371272.1(RAB11FIP5):​c.1535T>G​(p.Leu512Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: RAB11FIP5 NM_001371272.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

Genes affected

RAB11FIP5 (HGNC:24845): (RAB11 family interacting protein 5) Enables gamma-tubulin binding activity. Involved in cellular response to acidic pH; negative regulation of adiponectin secretion; and regulation of protein localization to cell surface. Located in centriolar satellite and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB11FIP5 (HGNC:):

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=0.27618724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB11FIP5	NM_001371272.1	c.1535T>G	p.Leu512Trp	missense_variant	3/6	ENST00000486777.7	NP_001358201.1
RAB11FIP5	NM_015470.3	c.1535T>G	p.Leu512Trp	missense_variant	3/5		NP_056285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB11FIP5	ENST00000486777.7	c.1535T>G	p.Leu512Trp	missense_variant	3/6	5	NM_001371272.1	ENSP00000489752.1
RAB11FIP5	ENST00000258098.6	c.1535T>G	p.Leu512Trp	missense_variant	3/5	1		ENSP00000258098.6
RAB11FIP5	ENST00000479196.1	n.246T>G		non_coding_transcript_exon_variant	1/2	3
RAB11FIP5	ENST00000493523.2	n.1444T>G		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Oct 20, 2024

The c.1535T>G (p.L512W) alteration is located in exon 3 (coding exon 3) of the RAB11FIP5 gene. This alteration results from a T to G substitution at nucleotide position 1535, causing the leucine (L) at amino acid position 512 to be replaced by a tryptophan (W). 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	Benign	0.21
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Benign	0.045	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.11
Sift	Uncertain	0.012	.;D
Sift4G	Uncertain	0.030	.;D
Polyphen		0.98	.;D
Vest4		0.42
MutPred		0.40		Gain of MoRF binding (P = 0.0363);Gain of MoRF binding (P = 0.0363);
MVP		0.75
MPC		0.65
ClinPred		0.88	D
GERP RS		3.5
Varity_R		0.050
gMVP		0.30

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: chr2-73315211;