3-159252782-C-G

Position:

• chr3-159252782-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042706.3(IQCJ):​c.130C>G​(p.Gln44Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: IQCJ NM_001042706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49

Genes affected

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

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]

ACMG classification

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=0.24051696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCJ	NM_001042706.3	c.130C>G	p.Gln44Glu	missense_variant	3/4	ENST00000397832.7	NP_001036171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCJ	ENST00000397832.7	c.130C>G	p.Gln44Glu	missense_variant	3/4	1	NM_001042706.3	ENSP00000380932.2
IQCJ-SCHIP1	ENST00000485419.7	c.130C>G	p.Gln44Glu	missense_variant	3/11	2		ENSP00000420182.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.130C>G (p.Q44E) alteration is located in exon 3 (coding exon 3) of the IQCJ gene. This alteration results from a C to G substitution at nucleotide position 130, causing the glutamine (Q) at amino acid position 44 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	.;T;.;.;.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.75	T;T;T;T;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;.;.;.;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.71	.;N;.;.;D;D
REVEL	Benign	0.084
Sift	Benign	0.094	.;T;.;.;D;D
Sift4G	Benign	0.17	.;T;.;.;T;T
Polyphen		0.86, 0.97	.;.;.;.;P;D
Vest4		0.46, 0.54, 0.58
MutPred		0.23		Loss of MoRF binding (P = 0.0536);Loss of MoRF binding (P = 0.0536);Loss of MoRF binding (P = 0.0536);.;Loss of MoRF binding (P = 0.0536);Loss of MoRF binding (P = 0.0536);
MVP		0.21
MPC		0.38, 0.030
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.060

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

Other links and lift over

dbSNP: rs1577116861; hg19: chr3-158970571;