10-118039251-C-T

Position:

• chr10-118039251-C-T

Variant summary

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

The NM_014904.3(RAB11FIP2):​c.986G>A​(p.Ser329Asn) 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. 15/21 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: 0.840

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=0.082258284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB11FIP2	NM_014904.3	c.986G>A	p.Ser329Asn	missense_variant	3/5	ENST00000355624.8
RAB11FIP2	NM_001330167.2	c.986G>A	p.Ser329Asn	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB11FIP2	ENST00000355624.8	c.986G>A	p.Ser329Asn	missense_variant	3/5	1	NM_014904.3	P1
RAB11FIP2	ENST00000369199.5	c.986G>A	p.Ser329Asn	missense_variant	3/6	1
	ENST00000451610.6	n.164-895C>T		intron_variant, non_coding_transcript_variant		2
RAB11FIP2	ENST00000483413.1	n.380G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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 21, 2022

The c.986G>A (p.S329N) alteration is located in exon 3 (coding exon 3) of the RAB11FIP2 gene. This alteration results from a G to A substitution at nucleotide position 986, causing the serine (S) at amino acid position 329 to be replaced by an asparagine (N). 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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.96	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.037
Sift	Benign	0.35	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.0010	B;.
Vest4		0.14
MutPred		0.19		Loss of phosphorylation at S329 (P = 0.0123);Loss of phosphorylation at S329 (P = 0.0123);
MVP		0.34
MPC		0.077
ClinPred		0.17	T
GERP RS		3.9
Varity_R		0.096
gMVP		0.17

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: rs1290889531; hg19: chr10-119798762;