Variant 3-159245843-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001042706.3(IQCJ):c.10G>A(p.Glu4Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000272 in 1,544,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

IQCJ
NM_001042706.3 missense, splice_region

Scores

Splicing: ADA: 0.9974

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

Variant links:

Genes affected

IQCJ (HGNC:32406): (IQ motif containing J)

IQCJ links:

IQCJ-SCHIP1 (HGNC:):

IQCJ-SCHIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCJ	NM_001042706.3 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant, splice_region_variant	2/4	ENST00000397832.7
IQCJ-SCHIP1	NM_001197113.2 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant, splice_region_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCJ	ENST00000397832.7 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant, splice_region_variant	2/4	1	NM_001042706.3		Q1A5X6-2
IQCJ	ENST00000451172.5 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant, splice_region_variant	2/5	1		P1	Q1A5X6-1
IQCJ	ENST00000482126.1 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant, splice_region_variant	2/4	1			Q1A5X6-3
IQCJ	ENST00000481796.1 linkuse as main transcript	n.371G>A		splice_region_variant, non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000424

AC:

AN:

164938

Hom.:

AF XY:

0.0000115

AC XY:

AN XY:

86694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000571

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000303

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000266

AC:

AN:

1392228

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

687054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000641

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000168

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000903

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.10G>A (p.E4K) alteration is located in exon 2 (coding exon 2) of the IQCJ gene. This alteration results from a G to A substitution at nucleotide position 10, causing the glutamic acid (E) at amino acid position 4 to be replaced by a lysine (K). 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

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.080

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T;T;T;T;T;T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.27

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.74

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Uncertain

0.54

Polyphen

1.0, 1.0

.;.;.;.;.;D;D;.

Vest4

0.53, 0.56, 0.69, 0.65, 0.67

MutPred

0.27

Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);

MVP

0.31

MPC

1.1, 0.030

ClinPred

0.81

GERP RS

5.5

Varity_R

0.84

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.90

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over