Variant 19-18257359-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001145304.2(IQCN):c.3925T>C(p.Ser1309Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.178

Variant links:

Genes affected

IQCN (HGNC:29350): (IQ motif containing N) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

IQCN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30397868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IQCN	NM_001145304.2 linkuse as main transcript	c.3925T>C	p.Ser1309Pro	missense_variant	4/4	ENST00000392413.5
IQCN	NM_025249.4 linkuse as main transcript	c.3364T>C	p.Ser1122Pro	missense_variant	4/4
IQCN	NM_001145305.2 linkuse as main transcript	c.3226T>C	p.Ser1076Pro	missense_variant	4/4
IQCN	XM_005260084.2 linkuse as main transcript	c.3925T>C	p.Ser1309Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCN	ENST00000392413.5 linkuse as main transcript	c.3925T>C	p.Ser1309Pro	missense_variant	4/4	1	NM_001145304.2	A2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.3364T>C	p.Ser1122Pro	missense_variant	4/4	1		P2	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.3226T>C	p.Ser1076Pro	missense_variant	4/4	2		A2	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.5260T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249360

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Cov.:

ExAC

AF:

0.00000824

AC:

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 29, 2024

The c.3925T>C (p.S1309P) alteration is located in exon 4 (coding exon 3) of the KIAA1683 gene. This alteration results from a T to C substitution at nucleotide position 3925, causing the serine (S) at amino acid position 1309 to be replaced by a proline (P). 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

Pathogenic

0.90

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;.;.

Eigen

Benign

0.12

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.54

T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

.;.;.;N

REVEL

Benign

0.21

Sift

Benign

0.12

.;.;.;T

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.98

.;D;.;.

Vest4

0.37

MutPred

0.54

.;Gain of catalytic residue at S1122 (P = 0.009);.;.;

MVP

0.30

MPC

0.80

ClinPred

0.77

GERP RS

0.91

Varity_R

0.24

gMVP

0.56

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