rs9509307

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006531.5(IFT88):c.1337G>A(p.Ser446Asn) variant causes a missense change. The variant allele was found at a frequency of 0.741 in 1,601,714 control chromosomes in the GnomAD database, including 444,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.70 ( 37816 hom., cov: 31)

Exomes 𝑓: 0.75 ( 407153 hom. )

Consequence

IFT88
NM_006531.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.19

Variant links:

Genes affected

IFT88 (HGNC:20606): (intraflagellar transport 88) This gene encodes a member of the tetratrico peptide repeat (TPR) family. The encoded protein is involved in cilium biogenesis. Mutations of a similar gene in mouse can cause polycystic kidney disease. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2017]

IFT88 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8165531E-6).

BP6

Variant 13-20631053-G-A is Benign according to our data. Variant chr13-20631053-G-A is described in ClinVar as [Benign]. Clinvar id is 402967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-20631053-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT88	NM_006531.5 link	c.1337G>A	p.Ser446Asn	missense_variant	Exon 16 of 26	ENST00000351808.10	NP_006522.2	Q13099-2A0A140VJL7B3KX42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT88	ENST00000351808.10 link	c.1337G>A	p.Ser446Asn	missense_variant	Exon 16 of 26	1	NM_006531.5	ENSP00000261632.5		Q13099-2

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105657

AN:

151906

Hom.:

37800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.749

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.885

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.726

Gnomad OTH

AF:

0.719

GnomAD3 exomes

AF:

0.770

AC:

193468

AN:

251276

Hom.:

76101

AF XY:

0.774

AC XY:

105169

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.530

Gnomad AMR exome

AF:

0.853

Gnomad ASJ exome

AF:

0.694

Gnomad EAS exome

AF:

0.997

Gnomad SAS exome

AF:

0.878

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.725

Gnomad OTH exome

AF:

0.741

GnomAD4 exome

AF:

0.746

AC:

1081023

AN:

1449690

Hom.:

407153

Cov.:

AF XY:

0.750

AC XY:

541777

AN XY:

722042

show subpopulations

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.843

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.872

Gnomad4 FIN exome

AF:

0.745

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.742

GnomAD4 genome

AF:

0.695

AC:

105719

AN:

152024

Hom.:

37816

Cov.:

AF XY:

0.704

AC XY:

52335

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.539

Gnomad4 AMR

AF:

0.778

Gnomad4 ASJ

AF:

0.687

Gnomad4 EAS

AF:

0.996

Gnomad4 SAS

AF:

0.885

Gnomad4 FIN

AF:

0.746

Gnomad4 NFE

AF:

0.727

Gnomad4 OTH

AF:

0.720

Alfa

AF:

0.718

Hom.:

50675

Bravo

AF:

0.688

TwinsUK

AF:

0.739

AC:

2739

ALSPAC

AF:

0.725

AC:

2794

ESP6500AA

AF:

0.535

AC:

2359

ESP6500EA

AF:

0.721

AC:

6202

ExAC

AF:

0.760

AC:

92275

Asia WGS

AF:

0.914

AC:

3178

AN:

3478

EpiCase

AF:

0.723

EpiControl

AF:

0.724

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0000018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

.;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.034

D;D

Polyphen

0.55

.;P

Vest4

0.21

MPC

0.052

ClinPred

0.035

GERP RS

4.6

Varity_R

0.29

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over