chr3-159262556-G-A

Variant names:

• chr3-159262556-G-A
• rs1186246085
• NM_001042706.3:c.164G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.29
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31744003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042706.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCJ	NM_001042706.3	MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 4 of 4	NP_001036171.1	Q1A5X6-2
	IQCJ-SCHIP1	NM_001197113.2		c.164G>A	p.Arg55Gln	missense	Exon 4 of 11	NP_001184042.1	B3KU38-1
	IQCJ-SCHIP1	NM_001197114.2		c.83G>A	p.Arg28Gln	missense	Exon 3 of 10	NP_001184043.1	B3KU38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCJ	ENST00000397832.7	TSL:1 MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 4 of 4	ENSP00000380932.2	Q1A5X6-2
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.164G>A	p.Arg55Gln	missense	Exon 4 of 11	ENSP00000420182.1	B3KU38-1
	IQCJ	ENST00000451172.5	TSL:1	c.164G>A	p.Arg55Gln	missense	Exon 4 of 5	ENSP00000402153.1	Q1A5X6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460620 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726496

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111288

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.76
MutPred		0.22		Gain of ubiquitination at K51 (P = 0.0414)
MVP		0.58
MPC		1.1
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.62
gMVP		0.16
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1186246085; hg19: chr3-158980345; COSMIC: COSV106560463;