Variant chr7-123496858-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_178827.5(IQUB):c.1072G>A(p.Val358Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,612,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

IQUB
NM_178827.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15618002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQUB	NM_178827.5 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant	7/13	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.1072G>A	p.Val358Ile	missense_variant	7/13	1	NM_178827.5	ENSP00000324882	P1	Q8NA54-1
IQUB	ENST00000466202.5 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant	7/13	1		ENSP00000417769	P1	Q8NA54-1
IQUB	ENST00000484508.5 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant, NMD_transcript_variant	7/14	2		ENSP00000417285		Q8NA54-2
IQUB	ENST00000469057.1 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant, NMD_transcript_variant	7/12	2		ENSP00000417636

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000280

AC:

AN:

250070

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000288

AC:

AN:

1460120

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726386

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000125

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.00

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

Alfa

AF:

0.0000824

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

Apr 25, 2022

The c.1072G>A (p.V358I) alteration is located in exon 7 (coding exon 6) of the IQUB gene. This alteration results from a G to A substitution at nucleotide position 1072, causing the valine (V) at amino acid position 358 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

Benign

0.19

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.012

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.026

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.99

D;D

Vest4

0.25

MVP

0.26

MPC

0.040

ClinPred

0.11

GERP RS

4.3

Varity_R

0.055

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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