Variant 3-159262556-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_001042706.3(IQCJ):c.164G>A(p.Arg55Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,620 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: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IQCJ
NM_001042706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29

Variant links:

Genes affected

IQCJ (HGNC:32406): (IQ motif containing J)

IQCJ links:

IQCJ-SCHIP1 (HGNC:38842): (IQCJ-SCHIP1 readthrough) This locus represents naturally occurring read-through transcription from the neighboring IQ motif containing J (IQCJ) and schwannomin interacting protein 1 (SCHIP1) genes. Alternative splicing results in multiple transcript variants that are composed of in-frame exons from each individual gene. The resulting fusion products are thought to be components of the multimolecular complexes of axon initial segments and nodes of Ranvier, and they may play a role in calcium-mediated responses. [provided by RefSeq, Oct 2010]

IQCJ-SCHIP1 links:

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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=0.31744003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCJ	NM_001042706.3 linkuse as main transcript	c.164G>A	p.Arg55Gln	missense_variant	4/4	ENST00000397832.7	NP_001036171.1	Q1A5X6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCJ	ENST00000397832.7 linkuse as main transcript	c.164G>A	p.Arg55Gln	missense_variant	4/4	1	NM_001042706.3	ENSP00000380932.2		Q1A5X6-2
IQCJ-SCHIP1	ENST00000485419.7 linkuse as main transcript	c.164G>A	p.Arg55Gln	missense_variant	4/11	2		ENSP00000420182.1		B3KU38-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460620

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726496

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:

0.00000270

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

Mar 20, 2024

The c.164G>A (p.R55Q) alteration is located in exon 4 (coding exon 4) of the IQCJ gene. This alteration results from a G to A substitution at nucleotide position 164, causing the arginine (R) at amino acid position 55 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

Benign

0.23

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.030

.;T;.;.;.;.;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.026

MetaRNN

Benign

0.32

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.8

.;.;.;.;.;L;L;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.38

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

REVEL

Benign

0.19

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.043

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

Polyphen

0.99, 1.0

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

Vest4

0.76

MutPred

0.22

.;Gain of ubiquitination at K51 (P = 0.0414);Gain of ubiquitination at K51 (P = 0.0414);.;.;Gain of ubiquitination at K51 (P = 0.0414);Gain of ubiquitination at K51 (P = 0.0414);.;

MVP

0.58

MPC

1.1, 0.029

ClinPred

0.99

GERP RS

5.5

Varity_R

0.62

gMVP

0.16

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

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