3-159252782-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:):

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	UniProt
IQCJ	NM_001042706.3	c.130C>G	p.Gln44Glu	missense_variant	3/4	ENST00000397832.7
IQCJ-SCHIP1	NM_001197113.2	c.130C>G	p.Gln44Glu	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCJ	ENST00000397832.7	c.130C>G	p.Gln44Glu	missense_variant	3/4	1	NM_001042706.3
IQCJ	ENST00000451172.5	c.130C>G	p.Gln44Glu	missense_variant	3/5	1		P1
IQCJ	ENST00000482126.1	c.74+6875C>G		intron_variant		1
IQCJ	ENST00000481796.1	n.435+6875C>G		intron_variant, non_coding_transcript_variant		4

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
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
MutationTaster	Benign	1.0	D;N;N;D;N
PrimateAI	Benign	0.40	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;