chr16-426220-G-C

Position:

• chr16-426220-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014700.4(RAB11FIP3):​c.214G>C​(p.Ala72Pro) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RAB11FIP3 NM_014700.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.410

Genes affected

RAB11FIP3 (HGNC:17224): (RAB11 family interacting protein 3) Proteins of the large Rab GTPase family (see RAB1A; MIM 179508) have regulatory roles in the formation, targeting, and fusion of intracellular transport vesicles. RAB11FIP3 is one of many proteins that interact with and regulate Rab GTPases (Hales et al., 2001 [PubMed 11495908]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055636346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB11FIP3	NM_014700.4	c.214G>C	p.Ala72Pro	missense_variant	1/14	ENST00000262305.9	NP_055515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB11FIP3	ENST00000262305.9	c.214G>C	p.Ala72Pro	missense_variant	1/14	1	NM_014700.4	ENSP00000262305
RAB11FIP3	ENST00000434585.6	c.214G>C	p.Ala72Pro	missense_variant	1/15	5		ENSP00000399644	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

May 29, 2024

The c.214G>C (p.A72P) alteration is located in exon 1 (coding exon 1) of the RAB11FIP3 gene. This alteration results from a G to C substitution at nucleotide position 214, causing the alanine (A) at amino acid position 72 to be replaced by a proline (P). 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	0.075
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.0090
Sift	Benign	0.11	T
Sift4G	Benign	0.27	T
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.093
MPC		1.3
ClinPred		0.048	T
GERP RS		-0.46
Varity_R		0.056
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs2054938654; hg19: chr16-476220;