Variant 7-123469320-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178827.5(IQUB):c.1475C>T(p.Thr492Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,609,308 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

IQUB
NM_178827.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

Variant links:

Genes affected

IQUB (HGNC:21995): (IQ motif and ubiquitin domain containing) Predicted to be involved in cilium assembly. Predicted to act upstream of or within smoothened signaling pathway. Predicted to be active in acrosomal vesicle and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

IQUB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.353088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQUB	NM_178827.5 linkuse as main transcript	c.1475C>T	p.Thr492Ile	missense_variant	9/13	ENST00000324698.11	NP_849149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQUB	ENST00000324698.11 linkuse as main transcript	c.1475C>T	p.Thr492Ile	missense_variant	9/13	1	NM_178827.5	ENSP00000324882	P1	Q8NA54-1
IQUB	ENST00000466202.5 linkuse as main transcript	c.1475C>T	p.Thr492Ile	missense_variant	9/13	1		ENSP00000417769	P1	Q8NA54-1
IQUB	ENST00000484508.5 linkuse as main transcript	c.1475C>T	p.Thr492Ile	missense_variant, NMD_transcript_variant	9/14	2		ENSP00000417285		Q8NA54-2
IQUB	ENST00000469057.1 linkuse as main transcript	c.*33C>T		3_prime_UTR_variant, NMD_transcript_variant	8/12	2		ENSP00000417636

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249760

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457220

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.1475C>T (p.T492I) alteration is located in exon 9 (coding exon 8) of the IQUB gene. This alteration results from a C to T substitution at nucleotide position 1475, causing the threonine (T) at amino acid position 492 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Benign

1.9

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.075

T;T

Polyphen

0.67

P;P

Vest4

0.58

MutPred

0.46

Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.27

MPC

0.065

ClinPred

0.96

GERP RS

4.7

Varity_R

0.70

gMVP

0.68

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