Variant 13-20615802-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006531.5(IFT88):c.1122G>A(p.Met374Ile) variant causes a missense change. The variant allele was found at a frequency of 0.137 in 1,587,320 control chromosomes in the GnomAD database, including 16,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2394 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14279 hom. )

Consequence

IFT88
NM_006531.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.19

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:

IFT88 (HGNC:):

IFT88 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 13-20615802-G-A is Benign according to our data. Variant chr13-20615802-G-A is described in ClinVar as [Benign]. Clinvar id is 402965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT88	NM_006531.5 linkuse as main transcript	c.1122G>A	p.Met374Ile	missense_variant	14/26	ENST00000351808.10	NP_006522.2	Q13099-2A0A140VJL7B3KX42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT88	ENST00000351808.10 linkuse as main transcript	c.1122G>A	p.Met374Ile	missense_variant	14/26	1	NM_006531.5	ENSP00000261632.5		Q13099-2

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24962

AN:

151888

Hom.:

2394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0634

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.126

AC:

30213

AN:

239968

Hom.:

2392

AF XY:

0.125

AC XY:

16222

AN XY:

129786

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0857

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.0000569

Gnomad SAS exome

AF:

0.0735

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.134

AC:

193041

AN:

1435314

Hom.:

14279

Cov.:

AF XY:

0.133

AC XY:

94966

AN XY:

714680

show subpopulations

Gnomad4 AFR exome

AF:

0.252

Gnomad4 AMR exome

AF:

0.0909

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.000280

Gnomad4 SAS exome

AF:

0.0780

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.164

AC:

24979

AN:

152006

Hom.:

2394

Cov.:

AF XY:

0.158

AC XY:

11715

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0635

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.149

Hom.:

4501

Bravo

AF:

0.170

TwinsUK

AF:

0.132

AC:

490

ALSPAC

AF:

0.148

AC:

571

ESP6500AA

AF:

0.248

AC:

1094

ESP6500EA

AF:

0.147

AC:

1264

ExAC

AF:

0.132

AC:

15962

Asia WGS

AF:

0.0400

AC:

140

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

0.16

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.090

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

D;D

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.011

Sift

Benign

0.18

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.023

.;B

Vest4

0.17

MutPred

0.34

.;Loss of disorder (P = 0.0696);

MPC

0.048

ClinPred

0.0065

GERP RS

4.7

Varity_R

0.15

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.27

Position offset: -9

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