3-159245888-G-A

Position:

• chr3-159245888-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042706.3(IQCJ):​c.55G>A​(p.Gly19Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000288 in 1,390,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: IQCJ NM_001042706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.34

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33485034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCJ	NM_001042706.3	c.55G>A	p.Gly19Arg	missense_variant	2/4	ENST00000397832.7	NP_001036171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCJ	ENST00000397832.7	c.55G>A	p.Gly19Arg	missense_variant	2/4	1	NM_001042706.3	ENSP00000380932.2
IQCJ-SCHIP1	ENST00000485419.7	c.55G>A	p.Gly19Arg	missense_variant	2/11	2		ENSP00000420182.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000288 AC: 4 AN: 1390706 Hom.: 0 Cov.: 29 AF XY: 0.00000291 AC XY: 2 AN XY: 686258

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: 0.00000374

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Aug 26, 2024

The c.55G>A (p.G19R) alteration is located in exon 2 (coding exon 2) of the IQCJ gene. This alteration results from a G to A substitution at nucleotide position 55, causing the glycine (G) at amino acid position 19 to be replaced by an arginine (R). 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	0.25
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;.;T;.;.;.;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;T;D;D;T;D;D;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.33	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.8	.;.;.;.;.;L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.74	.;N;D;.;.;D;D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	.;D;D;.;.;D;D;D
Sift4G	Uncertain	0.018	.;D;D;.;.;D;D;D
Polyphen		0.99, 1.0	.;.;.;.;.;D;D;.
Vest4		0.56, 0.60, 0.59, 0.64, 0.75
MutPred		0.31		Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP		0.068
MPC		1.1, 0.028
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.086

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr3-158963677;