Variant 13-20574386-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_006531.5(IFT88):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000598 in 1,606,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

IFT88
NM_006531.5 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

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 Pathogenic. Variant got 10 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT88	NM_006531.5 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	2/26	ENST00000351808.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT88	ENST00000351808.10 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	2/26	1	NM_006531.5	P1	Q13099-2
IFT88	ENST00000319980.10 linkuse as main transcript	c.28A>G	p.Met10Val	missense_variant	4/28	1			Q13099-1
IFT88	ENST00000389373.3 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

249890

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000557

AC:

AN:

1454012

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

723634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00132

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000547

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Nov 11, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with IFT88-related conditions. This variant is present in population databases (rs191277814, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 10 of the IFT88 protein (p.Met10Val). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.030

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;T;D

M_CAP

Benign

0.068

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Uncertain

-0.0047

MutationTaster

Benign

0.65

N;N;N;N

PROVEAN

Benign

-0.73

N;N;N

REVEL

Uncertain

0.48

Sift

Uncertain

0.013

D;D;D

Sift4G

Pathogenic

0.0

D;T;D

Polyphen

0.034

.;B;.

Vest4

0.82

MVP

0.80

MPC

0.077

ClinPred

0.12

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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