3-159252746-G-C

Variant summary

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

The NM_001042706.3(IQCJ):c.94G>C(p.Ala32Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: IQCJ NM_001042706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.241

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=0.073201716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCJ	NM_001042706.3	c.94G>C	p.Ala32Pro	missense_variant	3/4	ENST00000397832.7
IQCJ-SCHIP1	NM_001197113.2	c.94G>C	p.Ala32Pro	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCJ	ENST00000397832.7	c.94G>C	p.Ala32Pro	missense_variant	3/4	1	NM_001042706.3
IQCJ	ENST00000451172.5	c.94G>C	p.Ala32Pro	missense_variant	3/5	1		P1
IQCJ	ENST00000482126.1	c.74+6839G>C		intron_variant		1
IQCJ	ENST00000481796.1	n.435+6839G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000810 AC: 2 AN: 246874 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 133884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

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: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1459634 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000900

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000659 Hom.: 0

ExAC AF: 0.0000166 AC: 2

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

Apr 17, 2023

The c.94G>C (p.A32P) alteration is located in exon 3 (coding exon 3) of the IQCJ gene. This alteration results from a G to C substitution at nucleotide position 94, causing the alanine (A) at amino acid position 32 to be replaced by a proline (P). 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	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	7.3
Dann	Benign	0.92
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.67	T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.073	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N;N;D;N
PrimateAI	Benign	0.22	T
Polyphen		0.76, 0.26	.;.;.;.;P;B
Vest4		0.26, 0.26, 0.34
MutPred		0.29		Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);.;Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);
MVP		0.082
MPC		0.40, 0.0078
ClinPred		0.080	T
GERP RS		-1.2
Varity_R		0.20
gMVP		0.075

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: rs781023237; hg19: chr3-158970535;