Variant 19-18257404-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145304.2(IQCN):c.3880C>T(p.Pro1294Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000621 in 1,610,536 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000063 ( 1 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.586

Variant links:

Genes affected

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

IQCN links:

IQCN (HGNC:):

IQCN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13216668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCN	NM_001145304.2 linkuse as main transcript	c.3880C>T	p.Pro1294Ser	missense_variant	4/4	ENST00000392413.5	NP_001138776.1	Q9H0B3-4
IQCN	NM_025249.4 linkuse as main transcript	c.3319C>T	p.Pro1107Ser	missense_variant	4/4		NP_079525.1	Q9H0B3-1
IQCN	NM_001145305.2 linkuse as main transcript	c.3181C>T	p.Pro1061Ser	missense_variant	4/4		NP_001138777.1	Q9H0B3-5A0JP07
IQCN	XM_005260084.2 linkuse as main transcript	c.3880C>T	p.Pro1294Ser	missense_variant	4/4		XP_005260141.1	Q9H0B3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IQCN	ENST00000392413.5 linkuse as main transcript	c.3880C>T	p.Pro1294Ser	missense_variant	4/4	1	NM_001145304.2	ENSP00000376213.2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.3319C>T	p.Pro1107Ser	missense_variant	4/4	1		ENSP00000470780.1	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.3181C>T	p.Pro1061Ser	missense_variant	4/4	2		ENSP00000472912.1	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.5215C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

246802

Hom.:

AF XY:

0.0000521

AC XY:

AN XY:

134270

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000717

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000631

AC:

AN:

1458286

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

725426

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000774

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jun 25, 2024

The c.3880C>T (p.P1294S) alteration is located in exon 4 (coding exon 3) of the KIAA1683 gene. This alteration results from a C to T substitution at nucleotide position 3880, causing the proline (P) at amino acid position 1294 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

0.095

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.4

DANN

Benign

0.89

DEOGEN2

Benign

0.011

T;T;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.47

T;T;T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.76

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

.;.;.;N

REVEL

Benign

0.13

Sift

Benign

0.34

.;.;.;T

Sift4G

Benign

0.64

T;T;T;T

Polyphen

0.98

.;D;.;.

Vest4

0.083

MutPred

0.34

.;Gain of MoRF binding (P = 0.036);.;.;

MVP

0.49

MPC

0.18

ClinPred

0.24

GERP RS

2.1

Varity_R

0.022

gMVP

0.079

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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