10-118039018-G-A

Position:

• chr10-118039018-G-A

Variant summary

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

The NM_014904.3(RAB11FIP2):​c.1219C>T​(p.Pro407Ser) 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: RAB11FIP2 NM_014904.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.21

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4186027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB11FIP2	NM_014904.3	c.1219C>T	p.Pro407Ser	missense_variant	3/5	ENST00000355624.8	NP_055719.1
RAB11FIP2	NM_001330167.2	c.1219C>T	p.Pro407Ser	missense_variant	3/6		NP_001317096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB11FIP2	ENST00000355624.8	c.1219C>T	p.Pro407Ser	missense_variant	3/5	1	NM_014904.3	ENSP00000347839	P1
RAB11FIP2	ENST00000369199.5	c.1219C>T	p.Pro407Ser	missense_variant	3/6	1		ENSP00000358200
	ENST00000451610.6	n.164-1128G>A		intron_variant, non_coding_transcript_variant		2
RAB11FIP2	ENST00000483413.1	n.613C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 02, 2021

The c.1219C>T (p.P407S) alteration is located in exon 3 (coding exon 3) of the RAB11FIP2 gene. This alteration results from a C to T substitution at nucleotide position 1219, causing the proline (P) at amino acid position 407 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	0.74
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Uncertain	-0.053	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.87	N;N
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.10	T;T
Polyphen		1.0	D;.
Vest4		0.69
MutPred		0.42		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.52
MPC		0.44
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.26
gMVP		0.70

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: chr10-119798529;