3-159262579-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042706.3(IQCJ):c.187C>T(p.Arg63Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,510 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 (★). 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: 0.000012 (0 hom.)
• Consequence: IQCJ NM_001042706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.931

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=0.25581664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCJ	NM_001042706.3	c.187C>T	p.Arg63Trp	missense_variant	4/4	ENST00000397832.7
IQCJ-SCHIP1	NM_001197113.2	c.187C>T	p.Arg63Trp	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCJ	ENST00000397832.7	c.187C>T	p.Arg63Trp	missense_variant	4/4	1	NM_001042706.3
IQCJ	ENST00000451172.5	c.187C>T	p.Arg63Trp	missense_variant	4/5	1		P1
IQCJ	ENST00000482126.1	c.106C>T	p.Arg36Trp	missense_variant	3/4	1
IQCJ	ENST00000481796.1	n.467C>T		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000807 AC: 2 AN: 247780 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134556

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461510 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11 AN XY: 727012

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000164

EpiControl AF: 0.000119

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

Mar 11, 2022

The c.187C>T (p.R63W) alteration is located in exon 4 (coding exon 4) of the IQCJ gene. This alteration results from a C to T substitution at nucleotide position 187, causing the arginine (R) at amino acid position 63 to be replaced by a tryptophan (W). 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	0.29
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.070
Cadd	Uncertain	24
Dann	Pathogenic	1.0
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.60	T
MutationTaster	Benign	0.85	D;D;D;N;N
MutPred		0.21		Loss of helix (P = 0.028);
ClinPred		0.97	D
GERP RS		3.5

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

Publications

LitVar

Other links and lift over

dbSNP: rs766827460; hg19: chr3-158980368; COSMIC: COSV67331795;