Variant 7-123464961-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_178827.5(IQUB):c.1630G>A(p.Glu544Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,798 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: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IQUB
NM_178827.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQUB	NM_178827.5 linkuse as main transcript	c.1630G>A	p.Glu544Lys	missense_variant	10/13	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.1630G>A	p.Glu544Lys	missense_variant	10/13	1	NM_178827.5	ENSP00000324882	P1	Q8NA54-1
IQUB	ENST00000466202.5 linkuse as main transcript	c.1630G>A	p.Glu544Lys	missense_variant	10/13	1		ENSP00000417769	P1	Q8NA54-1
IQUB	ENST00000484508.5 linkuse as main transcript	c.1630G>A	p.Glu544Lys	missense_variant, NMD_transcript_variant	10/14	2		ENSP00000417285		Q8NA54-2
IQUB	ENST00000469057.1 linkuse as main transcript	c.*188G>A		3_prime_UTR_variant, NMD_transcript_variant	9/12	2		ENSP00000417636

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447798

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720244

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 26, 2022

The c.1630G>A (p.E544K) alteration is located in exon 10 (coding exon 9) of the IQUB gene. This alteration results from a G to A substitution at nucleotide position 1630, causing the glutamic acid (E) at amino acid position 544 to be replaced by a lysine (K). 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

0.98

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

T;T

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

3.1

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.9

D;D

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.98

MutPred

0.77

Gain of MoRF binding (P = 0.0148);Gain of MoRF binding (P = 0.0148);

MVP

0.85

MPC

0.20

ClinPred

1.0

GERP RS

5.4

Varity_R

0.88

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over