Genetic Variant RAB11FIP1:p.Ala1167Ser (chr8-37871303-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002814.3(RAB11FIP1):c.3499G>T(p.Ala1167Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1167T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RAB11FIP1
NM_001002814.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.429

Publications

3 publications found

Variant links:

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]

RAB11FIP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12128091).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002814.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP1	NM_001002814.3	MANE Select	c.3499G>T	p.Ala1167Ser	missense	Exon 4 of 6	NP_001002814.2	Q6WKZ4-4
	RAB11FIP1	NM_025151.5		c.1623-775G>T		intron	N/A	NP_079427.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB11FIP1	ENST00000330843.9	TSL:1 MANE Select	c.3499G>T	p.Ala1167Ser	missense	Exon 4 of 6	ENSP00000331342.4	Q6WKZ4-4
RAB11FIP1	ENST00000287263.8	TSL:1	c.1623-775G>T		intron	N/A	ENSP00000287263.4	Q6WKZ4-3
RAB11FIP1	ENST00000522727.5	TSL:1	c.1179-775G>T		intron	N/A	ENSP00000430009.1	E7EX40

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458824

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725770

show subpopulations

African (AFR)

AF:

0.0000900

AC:

AN:

33322

American (AMR)

AF:

0.00

AC:

AN:

44166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25856

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

85880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5494

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110856

Other (OTH)

AF:

0.00

AC:

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.0

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.58

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

PhyloP100

0.43

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.89

REVEL

Benign

0.086

Sift

Benign

0.046

Sift4G

Benign

0.064

Polyphen

0.45

Vest4

0.081

MVP

0.45

MPC

0.25

ClinPred

0.43

GERP RS

0.33

Varity_R

0.097

gMVP

0.079

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over