X-53234582-C-T

Position:

chrX-53234582-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001111125.3(IQSEC2):c.4104G>A(p.Leu1368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,118,294 control chromosomes in the GnomAD database, including 1,164 homozygotes. There are 3,431 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 651 hom., 1583 hem., cov: 20)

Exomes 𝑓: 0.0071 ( 513 hom. 1848 hem. )

Consequence

IQSEC2
NM_001111125.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0530

Variant links:

Genes affected

IQSEC2 (HGNC:29059): (IQ motif and Sec7 domain ArfGEF 2) This gene encodes a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. The encoded protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates including ARF1 and ARF6. Mutations in this gene have been implicated in nonsyndromic X-linked cognitive disability. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

IQSEC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant X-53234582-C-T is Benign according to our data. Variant chrX-53234582-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.053 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC2	NM_001111125.3 linkuse as main transcript	c.4104G>A	p.Leu1368=	synonymous_variant	15/15	ENST00000642864.1	NP_001104595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC2	ENST00000642864.1 linkuse as main transcript	c.4104G>A	p.Leu1368=	synonymous_variant	15/15		NM_001111125.3	ENSP00000495726	P1	Q5JU85-2

Frequencies

GnomAD3 genomes

AF:

0.0668

AC:

7131

AN:

106704

Hom.:

653

Cov.:

AF XY:

0.0530

AC XY:

1570

AN XY:

29610

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.00536

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000890

Gnomad OTH

AF:

0.0519

GnomAD3 exomes

AF:

0.0221

AC:

1677

AN:

75764

Hom.:

119

AF XY:

0.0196

AC XY:

387

AN XY:

19772

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.00343

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000308

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000791

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.00708

AC:

7164

AN:

1011557

Hom.:

513

Cov.:

AF XY:

0.00577

AC XY:

1848

AN XY:

320513

show subpopulations

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.00540

Gnomad4 EAS exome

AF:

0.0000374

Gnomad4 SAS exome

AF:

0.000604

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000438

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0669

AC:

7138

AN:

106737

Hom.:

651

Cov.:

AF XY:

0.0534

AC XY:

1583

AN XY:

29653

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.00536

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000890

Gnomad4 OTH

AF:

0.0513

Alfa

AF:

0.0351

Hom.:

215

Bravo

AF:

0.0786

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 15, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 31, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 08, 2013	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 20, 2017	- -

Intellectual disability, X-linked 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.5

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

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