Genetic Variant IFT22:p.Asn89Ile (chr7-101316483-T-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022777.4(IFT22):c.266A>T(p.Asn89Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000644 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

IFT22
NM_022777.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

IFT22 (HGNC:21895): (intraflagellar transport 22) Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport. Predicted to be located in ciliary tip. Predicted to be part of intraciliary transport particle B. Predicted to be active in endomembrane system. [provided by Alliance of Genome Resources, Apr 2022]

IFT22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT22	NM_022777.4 link	c.266A>T	p.Asn89Ile	missense_variant	Exon 4 of 5	ENST00000315322.10	NP_073614.1	Q9H7X7-1A0A024QYV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT22	ENST00000315322.10 link	c.266A>T	p.Asn89Ile	missense_variant	Exon 4 of 5	1	NM_022777.4	ENSP00000320359.4		Q9H7X7-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152112

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:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000159

AC:

AN:

251488

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000672

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74432

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:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000103

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.266A>T (p.N89I) alteration is located in exon 4 (coding exon 4) of the IFT22 gene. This alteration results from a A to T substitution at nucleotide position 266, causing the asparagine (N) at amino acid position 89 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

.;.;T;.;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;.;D;.;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.86

D;D;D;D;D

MetaSVM

Uncertain

0.35

MutationAssessor

Pathogenic

3.0

.;.;M;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-7.5

.;D;D;D;D

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

.;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

0.99, 1.0

.;.;D;.;D

Vest4

0.87

MVP

0.69

MPC

1.0

ClinPred

0.92

GERP RS

4.9

Varity_R

0.77

gMVP

0.77

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

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