Variant 3-159252746-G-C 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_001042706.3(IQCJ):c.94G>C(p.Ala32Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

IQCJ
NM_001042706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.241

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073201716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCJ	NM_001042706.3 linkuse as main transcript	c.94G>C	p.Ala32Pro	missense_variant	3/4	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.94G>C	p.Ala32Pro	missense_variant	3/4	1	NM_001042706.3	ENSP00000380932.2		Q1A5X6-2
IQCJ-SCHIP1	ENST00000485419.7 linkuse as main transcript	c.94G>C	p.Ala32Pro	missense_variant	3/11	2		ENSP00000420182.1		B3KU38-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000810

AC:

AN:

246874

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

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:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1459634

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

ExAC

AF:

0.0000166

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 17, 2023

The c.94G>C (p.A32P) alteration is located in exon 3 (coding exon 3) of the IQCJ gene. This alteration results from a G to C substitution at nucleotide position 94, causing the alanine (A) at amino acid position 32 to be replaced by a proline (P). 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

-0.24

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.3

DANN

Benign

0.92

DEOGEN2

Benign

0.014

.;T;.;.;.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.67

T;T;T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.073

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;.;.;.;L;L

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.090

.;N;.;.;N;N

REVEL

Benign

0.056

Sift

Benign

0.054

.;T;.;.;T;T

Sift4G

Benign

0.16

.;T;.;.;T;T

Polyphen

0.76, 0.26

.;.;.;.;P;B

Vest4

0.26, 0.26, 0.34

MutPred

0.29

Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);.;Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);

MVP

0.082

MPC

0.40, 0.0078

ClinPred

0.080

GERP RS

-1.2

Varity_R

0.20

gMVP

0.075

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