8-37871554-G-C

Variant names:

• chr8-37871554-G-C
• NM_001002814.3:c.3248C>G

Variant summary

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

The NM_001002814.3(RAB11FIP1):​c.3248C>G​(p.Pro1083Arg) 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: RAB11FIP1 NM_001002814.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.25

Genes affected

RAB11FIP1 (HGNC:30265): (RAB11 family interacting protein 1) This gene encodes one of the Rab11-family interacting proteins (Rab11-FIPs), which play a role in the Rab-11 mediated recycling of vesicles. The encoded protein may be involved in endocytic sorting, trafficking of proteins including integrin subunits and epidermal growth factor receptor (EGFR), and transport between the recycling endosome and the trans-Golgi network. Alternative splicing results in multiple transcript variants. A pseudogene is described on the X chromosome. [provided by RefSeq, Dec 2013]

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=0.08200461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP1	NM_001002814.3	c.3248C>G	p.Pro1083Arg	missense_variant	Exon 4 of 6	ENST00000330843.9	NP_001002814.2
RAB11FIP1	XM_017013869.2	c.3248C>G	p.Pro1083Arg	missense_variant	Exon 4 of 4		XP_016869358.1
RAB11FIP1	NM_025151.5	c.1623-1026C>G		intron_variant	Intron 3 of 4		NP_079427.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB11FIP1	ENST00000330843.9	c.3248C>G	p.Pro1083Arg	missense_variant	Exon 4 of 6	1	NM_001002814.3	ENSP00000331342.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3248C>G (p.P1083R) alteration is located in exon 4 (coding exon 4) of the RAB11FIP1 gene. This alteration results from a C to G substitution at nucleotide position 3248, causing the proline (P) at amino acid position 1083 to be replaced by an arginine (R). 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	0.095
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.83
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.048
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.027	D
Polyphen		0.43	B
Vest4		0.18
MutPred		0.25		Loss of glycosylation at P1083 (P = 0.0256);
MVP		0.28
MPC		0.29
ClinPred		0.53	D
GERP RS		-0.79
Varity_R		0.063
gMVP		0.074

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: chr8-37729072;