Variant 7-2572312-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152558.5(IQCE):c.380G>A(p.Arg127His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,613,774 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000077 ( 1 hom. )

Consequence

IQCE
NM_152558.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.685

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]

IQCE links:

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=0.044916183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCE	NM_152558.5 linkuse as main transcript	c.380G>A	p.Arg127His	missense_variant	5/22	ENST00000402050.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCE	ENST00000402050.7 linkuse as main transcript	c.380G>A	p.Arg127His	missense_variant	5/22	1	NM_152558.5	A2	Q6IPM2-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000173

AC:

AN:

248792

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.0000886

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000766

AC:

112

AN:

1461552

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

727064

show subpopulations

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:

0.000209

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000412

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 04, 2024

The c.380G>A (p.R127H) alteration is located in exon 5 (coding exon 5) of the IQCE gene. This alteration results from a G to A substitution at nucleotide position 380, causing the arginine (R) at amino acid position 127 to be replaced by a histidine (H). 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

0.088

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.032

.;T;T;.;T;.;.;.;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.76

T;T;T;T;T;T;T;.;.;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.045

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

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

.;L;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

.;N;N;N;.;N;.;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.039

.;D;D;D;.;D;.;D;T;T

Sift4G

Benign

0.14

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

Polyphen

0.77

P;B;.;P;.;.;.;P;.;.

Vest4

0.18

MVP

0.52

MPC

0.15

ClinPred

0.037

GERP RS

0.94

Varity_R

0.045

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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