3-159262580-G-C

Variant names:

• chr3-159262580-G-C
• rs375080915
• NM_001042706.3:c.188G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001042706.3(IQCJ):​c.188G>C​(p.Arg63Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R63Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IQCJ NM_001042706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.188G>C	p.Arg63Pro	missense	Exon 4 of 4	NP_001036171.1	Q1A5X6-2
	IQCJ-SCHIP1	NM_001197113.2		c.188G>C	p.Arg63Pro	missense	Exon 4 of 11	NP_001184042.1	B3KU38-1
	IQCJ-SCHIP1	NM_001197114.2		c.107G>C	p.Arg36Pro	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.188G>C	p.Arg63Pro	missense	Exon 4 of 4	ENSP00000380932.2	Q1A5X6-2
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.188G>C	p.Arg63Pro	missense	Exon 4 of 11	ENSP00000420182.1	B3KU38-1
	IQCJ	ENST00000451172.5	TSL:1	c.188G>C	p.Arg63Pro	missense	Exon 4 of 5	ENSP00000402153.1	Q1A5X6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461498 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727010

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111764

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.82	N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.80
MutPred		0.17		Loss of MoRF binding (P = 0.0079)
MVP		0.68
MPC		1.2
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.24
Mutation Taster		=80/20	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: rs375080915; hg19: chr3-158980369;