dbSNP rs1555576369: IFT20:p.Glu66Gln (chr17-28330460-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001267776.2(IFT20):c.196G>C(p.Glu66Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IFT20
NM_001267776.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92

Variant links:

Genes affected

IFT20 (HGNC:30989): (intraflagellar transport 20) This gene encodes a intraflagellar transport protein important for intracellular transport. The encoded protein forms part of a complex involved in trafficking of proteins from the Golgi body, including recycling of immune signalling components (Finetti et al., PubMed: 19855387). This gene is part of a complex set of sense-antisense loci that may be co-regulated. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome 14.[provided by RefSeq, Jun 2012]

IFT20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT20	NM_001267776.2 link	c.196G>C	p.Glu66Gln	missense_variant	Exon 3 of 5	ENST00000395418.8	NP_001254705.1	Q8IY31-1A0A024QZ08

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT20	ENST00000395418.8 link	c.196G>C	p.Glu66Gln	missense_variant	Exon 3 of 5	1	NM_001267776.2	ENSP00000378809.3		Q8IY31-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726992

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.196G>C (p.E66Q) alteration is located in exon 3 (coding exon 2) of the IFT20 gene. This alteration results from a G to C substitution at nucleotide position 196, causing the glutamic acid (E) at amino acid position 66 to be replaced by a glutamine (Q). 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

0.82

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

.;.;.;.;D;.;D;T;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

D;D;D;D;.;D;D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.73

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

3.3

.;M;.;M;M;.;M;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.1

.;.;.;N;D;.;.;.;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0070

.;.;.;D;D;.;.;.;.

Sift4G

Uncertain

0.015

D;D;D;D;D;D;D;D;D

Polyphen

1.0, 0.99, 0.96

.;.;.;D;D;D;D;.;.

Vest4

0.65

MutPred

0.57

Loss of ubiquitination at K71 (P = 0.0302);Loss of ubiquitination at K71 (P = 0.0302);.;Loss of ubiquitination at K71 (P = 0.0302);Loss of ubiquitination at K71 (P = 0.0302);.;Loss of ubiquitination at K71 (P = 0.0302);.;.;

MVP

0.55

MPC

0.19

ClinPred

0.95

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.65

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