Variant chr19-18257436-C-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.3848G>T(p.Trp1283Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,609,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.308

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.097424835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IQCN	NM_001145304.2 linkuse as main transcript	c.3848G>T	p.Trp1283Leu	missense_variant	4/4	ENST00000392413.5
IQCN	NM_025249.4 linkuse as main transcript	c.3287G>T	p.Trp1096Leu	missense_variant	4/4
IQCN	NM_001145305.2 linkuse as main transcript	c.3149G>T	p.Trp1050Leu	missense_variant	4/4
IQCN	XM_005260084.2 linkuse as main transcript	c.3848G>T	p.Trp1283Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCN	ENST00000392413.5 linkuse as main transcript	c.3848G>T	p.Trp1283Leu	missense_variant	4/4	1	NM_001145304.2	A2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.3287G>T	p.Trp1096Leu	missense_variant	4/4	1		P2	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.3149G>T	p.Trp1050Leu	missense_variant	4/4	2		A2	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.5183G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

245124

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133506

show subpopulations

Gnomad AFR exome

AF:

0.000317

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1457230

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724884

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000199

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

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

Sep 01, 2021

The c.3848G>T (p.W1283L) alteration is located in exon 4 (coding exon 3) of the KIAA1683 gene. This alteration results from a G to T substitution at nucleotide position 3848, causing the tryptophan (W) at amino acid position 1283 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.17

T;T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.40

T;T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.097

T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.0

.;.;.;D

REVEL

Benign

0.077

Sift

Benign

0.17

.;.;.;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.18

.;B;.;.

Vest4

0.34

MVP

0.076

MPC

0.32

ClinPred

0.19

GERP RS

0.53

Varity_R

0.076

gMVP

0.11

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