dbSNP rs782304436: IQSEC3:p.Ala243Asp (chr12-125737-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170738.2(IQSEC3):c.728C>A(p.Ala243Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A243G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IQSEC3
NM_001170738.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.718

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]

IQSEC3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13985491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC3	NM_001170738.2 link	c.728C>A	p.Ala243Asp	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
IQSEC3	ENST00000538872.6 link	c.728C>A	p.Ala243Asp	missense_variant	Exon 3 of 14	5	NM_001170738.2	ENSP00000437554.1		Q9UPP2-1
IQSEC3	ENST00000382841.2 link	c.-6-12530C>A		intron_variant	Intron 2 of 12	2		ENSP00000372292.2		Q9UPP2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000781

AC:

AN:

128010

AF XY:

0.0000143

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1372736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677204

African (AFR)

AF:

0.00

AC:

AN:

30576

American (AMR)

AF:

0.00

AC:

AN:

33794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22950

East Asian (EAS)

AF:

0.00

AC:

AN:

36448

South Asian (SAS)

AF:

0.00

AC:

AN:

75610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076990

Other (OTH)

AF:

0.00

AC:

AN:

57234

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000175

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0091

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.46

PhyloP100

0.72

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.89

REVEL

Benign

0.18

Sift

Benign

0.39

Sift4G

Benign

0.56

Vest4

0.21

MutPred

0.17

Loss of helix (P = 0.0104);

MVP

0.37

MPC

0.60

ClinPred

0.14

GERP RS

3.8

Varity_R

0.10

gMVP

0.35

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over