NM_001170738.2:c.712G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001170738.2(IQSEC3):​c.712G>T​(p.Ala238Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IQSEC3
NM_001170738.2 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Publications

0 publications found
Variant links:
Genes affected
IQSEC3 (HGNC:29193): (IQ motif and Sec7 domain ArfGEF 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of small GTPase mediated signal transduction. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18468961).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IQSEC3NM_001170738.2 linkc.712G>T p.Ala238Ser missense_variant Exon 3 of 14 ENST00000538872.6 NP_001164209.1 Q9UPP2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IQSEC3ENST00000538872.6 linkc.712G>T p.Ala238Ser missense_variant Exon 3 of 14 5 NM_001170738.2 ENSP00000437554.1 Q9UPP2-1
IQSEC3ENST00000382841.2 linkc.-6-12546G>T intron_variant Intron 2 of 12 2 ENSP00000372292.2 Q9UPP2-2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152200
Hom.:
0
Cov.:
33
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1379060
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
681112
African (AFR)
AF:
0.00
AC:
0
AN:
30564
American (AMR)
AF:
0.00
AC:
0
AN:
34636
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22780
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37044
South Asian (SAS)
AF:
0.00
AC:
0
AN:
75672
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34256
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5476
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1081144
Other (OTH)
AF:
0.00
AC:
0
AN:
57488
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152200
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74362
African (AFR)
AF:
0.00
AC:
0
AN:
41448
American (AMR)
AF:
0.00
AC:
0
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2094

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 13, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.712G>T (p.A238S) alteration is located in exon 3 (coding exon 3) of the IQSEC3 gene. This alteration results from a G to T substitution at nucleotide position 712, causing the alanine (A) at amino acid position 238 to be replaced by a serine (S). 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
0.083
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0078
T
Eigen
Benign
0.072
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.54
T
M_CAP
Pathogenic
0.39
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.81
L
PhyloP100
2.1
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.030
N
REVEL
Benign
0.15
Sift
Benign
0.066
T
Sift4G
Benign
0.63
T
Vest4
0.23
MutPred
0.16
Gain of phosphorylation at A238 (P = 0.0189);
MVP
0.69
MPC
0.42
ClinPred
0.23
T
GERP RS
4.7
Varity_R
0.085
gMVP
0.15
Mutation Taster
=94/6
polymorphism

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

Other links and lift over

hg19: chr12-234887; API