7-2572268-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152558.5(IQCE):ā€‹c.336C>Gā€‹(p.Asp112Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,110 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

IQCE
NM_152558.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.205
Variant links:
Genes affected
IQCE (HGNC:29171): (IQ motif containing E) Involved in limb morphogenesis. Predicted to be extrinsic component of membrane. Predicted to be part of plasma membrane protein complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.010669172).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IQCENM_152558.5 linkuse as main transcriptc.336C>G p.Asp112Glu missense_variant 5/22 ENST00000402050.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IQCEENST00000402050.7 linkuse as main transcriptc.336C>G p.Asp112Glu missense_variant 5/221 NM_152558.5 A2Q6IPM2-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152272
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000176
AC:
44
AN:
249504
Hom.:
0
AF XY:
0.0000813
AC XY:
11
AN XY:
135374
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00119
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:
0.00
Gnomad OTH exome
AF:
0.000495
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1461838
Hom.:
0
Cov.:
33
AF XY:
0.0000220
AC XY:
16
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00110
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.000174
AC:
21

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 submitterclinical testingAmbry GeneticsMay 31, 2024The c.336C>G (p.D112E) alteration is located in exon 5 (coding exon 5) of the IQCE gene. This alteration results from a C to G substitution at nucleotide position 336, causing the aspartic acid (D) at amino acid position 112 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
0.14
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
10
DANN
Benign
0.64
DEOGEN2
Benign
0.0089
.;T;T;.;T;.;.;.;.;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.57
T;T;T;T;T;T;T;.;.;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.011
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
.;L;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.69
.;N;N;N;.;N;.;N;N;N
REVEL
Benign
0.057
Sift
Benign
1.0
.;T;T;T;.;T;.;T;T;T
Sift4G
Benign
0.77
T;T;T;T;T;T;T;T;T;T
Polyphen
0.43
B;P;.;P;.;.;.;B;.;.
Vest4
0.055
MutPred
0.27
.;Gain of MoRF binding (P = 0.1931);Gain of MoRF binding (P = 0.1931);.;Gain of MoRF binding (P = 0.1931);.;.;.;.;.;
MVP
0.27
MPC
0.14
ClinPred
0.033
T
GERP RS
1.1
Varity_R
0.042
gMVP
0.070

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

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

Other links and lift over

dbSNP: rs758451596; hg19: chr7-2611902; API