10-118039404-A-G

Position:

• chr10-118039404-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014904.3(RAB11FIP2):​c.833T>C​(p.Phe278Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB11FIP2 NM_014904.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30

Genes affected

RAB11FIP2 (HGNC:29152): (RAB11 family interacting protein 2) Enables protein homodimerization activity and protein kinase binding activity. Involved in several processes, including TRAM-dependent toll-like receptor 4 signaling pathway; phagocytosis; and positive regulation of GTPase activity. Located in endosome; nucleoplasm; and phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13895875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB11FIP2	NM_014904.3	c.833T>C	p.Phe278Ser	missense_variant	3/5	ENST00000355624.8
RAB11FIP2	NM_001330167.2	c.833T>C	p.Phe278Ser	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB11FIP2	ENST00000355624.8	c.833T>C	p.Phe278Ser	missense_variant	3/5	1	NM_014904.3	P1
RAB11FIP2	ENST00000369199.5	c.833T>C	p.Phe278Ser	missense_variant	3/6	1
	ENST00000451610.6	n.164-742A>G		intron_variant, non_coding_transcript_variant		2
RAB11FIP2	ENST00000483413.1	n.227T>C		non_coding_transcript_exon_variant	2/2	2

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

Jan 26, 2022

The c.833T>C (p.F278S) alteration is located in exon 3 (coding exon 3) of the RAB11FIP2 gene. This alteration results from a T to C substitution at nucleotide position 833, causing the phenylalanine (F) at amino acid position 278 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	Benign	0.080
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0091	T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	0.96	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	1.8	N;N
REVEL	Benign	0.25
Sift	Benign	0.078	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.0	B;.
Vest4		0.43
MutPred		0.27		Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);
MVP		0.55
MPC		0.15
ClinPred		0.38	T
GERP RS		4.5
Varity_R		0.071
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-119798915;