rs773854204

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-101321685-C-A
• chr7-101321685-C-G
• chr7-101321685-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130821.3(IFT22):​c.-238G>T 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 0.00000207 in 1,451,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IFT22 NM_001130821.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3864532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130821.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT22	NM_022777.4	MANE Select	c.25G>T	p.Val9Leu	missense	Exon 1 of 5	NP_073614.1	Q9H7X7-1
	IFT22	NM_001130821.3		c.-238G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001124293.1	Q9H7X7-3
	IFT22	NM_001130822.3		c.-130G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001124294.1	Q9H7X7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT22	ENST00000315322.10	TSL:1 MANE Select	c.25G>T	p.Val9Leu	missense	Exon 1 of 5	ENSP00000320359.4	Q9H7X7-1
	IFT22	ENST00000437644.2	TSL:1	c.25G>T	p.Val9Leu	missense	Exon 1 of 4	ENSP00000390770.2	Q9H7X7-2
	IFT22	ENST00000468833.1	TSL:1	n.106G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000433 AC: 1 AN: 230880 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451292 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721218

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33208

American (AMR) AF: 0.00 AC: 0 AN: 43054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25780

East Asian (EAS) AF: 0.00 AC: 0 AN: 39238

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107330

Other (OTH) AF: 0.00 AC: 0 AN: 59914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.96	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.93	N
REVEL	Uncertain	0.30
Sift	Benign	0.25	T
Sift4G	Benign	0.22	T
Polyphen		0.015	B
Vest4		0.44
MutPred		0.50		Gain of ubiquitination at K5 (P = 0.1047)
MVP		0.42
MPC		0.41
ClinPred		0.83	D
GERP RS		5.6
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.32
gMVP		0.53
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs773854204; hg19: chr7-100964966;