Genetic Variant NM_001002814.3:c.3208A>T (chr8-37871594-T-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.3208A>T(p.Ser1070Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RAB11FIP1
NM_001002814.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.497

Publications

0 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=0.097855836).

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.3208A>T	p.Ser1070Cys	missense	Exon 4 of 6	NP_001002814.2	Q6WKZ4-4
	RAB11FIP1	NM_025151.5		c.1623-1066A>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.3208A>T	p.Ser1070Cys	missense	Exon 4 of 6	ENSP00000331342.4	Q6WKZ4-4
RAB11FIP1	ENST00000287263.8	TSL:1	c.1623-1066A>T		intron	N/A	ENSP00000287263.4	Q6WKZ4-3
RAB11FIP1	ENST00000522727.5	TSL:1	c.1179-1066A>T		intron	N/A	ENSP00000430009.1	E7EX40

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449948

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33166

American (AMR)

AF:

0.00

AC:

AN:

43868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104234

Other (OTH)

AF:

0.00

AC:

AN:

59768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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.:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.45

M_CAP

Benign

0.017

MetaRNN

Benign

0.098

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.50

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Uncertain

0.013

Sift4G

Benign

0.061

Polyphen

0.82

Vest4

0.057

MutPred

0.17

Loss of phosphorylation at S1070 (P = 0.0034)

MVP

0.36

MPC

0.14

ClinPred

0.21

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.086

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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