7-101315256-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022777.4(IFT22):​c.436G>A​(p.Val146Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IFT22
NM_022777.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2251986).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFT22NM_022777.4 linkc.436G>A p.Val146Met missense_variant Exon 5 of 5 ENST00000315322.10 NP_073614.1 Q9H7X7-1A0A024QYV3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFT22ENST00000315322.10 linkc.436G>A p.Val146Met missense_variant Exon 5 of 5 1 NM_022777.4 ENSP00000320359.4 Q9H7X7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727242
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.436G>A (p.V146M) alteration is located in exon 5 (coding exon 5) of the IFT22 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the valine (V) at amino acid position 146 to be replaced by a methionine (M). 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
Benign
0.22
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.074
.;.;T;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.96
D;.;D;.;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.23
T;T;T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.4
.;.;M;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.6
.;N;N;N;N
REVEL
Benign
0.20
Sift
Uncertain
0.0050
.;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;T;D;D
Polyphen
1.0, 0.99
.;.;D;.;D
Vest4
0.11
MutPred
0.52
.;.;Gain of helix (P = 0.0854);.;.;
MVP
0.22
MPC
0.86
ClinPred
0.98
D
GERP RS
3.6
Varity_R
0.12
gMVP
0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-100958537; API