chr7-101321685-C-T

Variant names:

• chr7-101321685-C-T
• rs773854204
• NM_022777.4:c.25G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001130821.3(IFT22):​c.-238G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,451,294 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: IFT22 NM_001130821.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT22	NM_022777.4	c.25G>A	p.Val9Met	missense_variant	Exon 1 of 5	ENST00000315322.10	NP_073614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT22	ENST00000315322.10	c.25G>A	p.Val9Met	missense_variant	Exon 1 of 5	1	NM_022777.4	ENSP00000320359.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1451294 Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3 AN XY: 721220

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: 0.0000472

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25G>A (p.V9M) alteration is located in exon 1 (coding exon 1) of the IFT22 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the valine (V) at amino acid position 9 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	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.61
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.98	D;D
Vest4		0.56
MutPred		0.59		Gain of ubiquitination at K5 (P = 0.0797);Gain of ubiquitination at K5 (P = 0.0797);
MVP		0.57
MPC		0.90
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.31
gMVP		0.60

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

Other links and lift over

dbSNP: rs773854204; hg19: chr7-100964966;