3-159265324-A-G

Variant names:

• chr3-159265324-A-G
• ENST00000451172.5:c.401A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042705.3(IQCJ):​c.401A>G​(p.Gln134Arg) 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. 15/20 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)
• Consequence: IQCJ NM_001042705.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07009184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042705.3. 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_001042705.3		c.401A>G	p.Gln134Arg	missense	Exon 5 of 5	NP_001036170.1	Q1A5X6-1
	IQCJ	NM_001197100.2		c.320A>G	p.Gln107Arg	missense	Exon 4 of 4	NP_001184029.1	Q1A5X6-3
	IQCJ-SCHIP1	NM_001197113.2		c.291+2641A>G		intron	N/A	NP_001184042.1	B3KU38-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCJ	ENST00000451172.5	TSL:1	c.401A>G	p.Gln134Arg	missense	Exon 5 of 5	ENSP00000402153.1	Q1A5X6-1
	IQCJ	ENST00000482126.1	TSL:1	c.320A>G	p.Gln107Arg	missense	Exon 4 of 4	ENSP00000418141.1	Q1A5X6-3
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.291+2641A>G		intron	N/A	ENSP00000420182.1	B3KU38-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.091
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.26
DANN	Benign	0.58
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.4
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.023
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.23		Gain of MoRF binding (P = 0.0646)
MVP		0.085
MPC		0.0059
ClinPred		0.19	T
GERP RS		-5.2
Varity_R		0.16
gMVP		0.032
Mutation Taster		=99/1	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

hg19: chr3-158983113;