Variant 19-18257449-C-T 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.3835G>A(p.Gly1279Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,608,344 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.39

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=0.13251391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCN	NM_001145304.2 linkuse as main transcript	c.3835G>A	p.Gly1279Arg	missense_variant	4/4	ENST00000392413.5	NP_001138776.1	Q9H0B3-4
IQCN	NM_025249.4 linkuse as main transcript	c.3274G>A	p.Gly1092Arg	missense_variant	4/4		NP_079525.1	Q9H0B3-1
IQCN	NM_001145305.2 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant	4/4		NP_001138777.1	Q9H0B3-5A0JP07
IQCN	XM_005260084.2 linkuse as main transcript	c.3835G>A	p.Gly1279Arg	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.3835G>A	p.Gly1279Arg	missense_variant	4/4	1	NM_001145304.2	ENSP00000376213.2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.3274G>A	p.Gly1092Arg	missense_variant	4/4	1		ENSP00000470780.1	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant	4/4	2		ENSP00000472912.1	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.5170G>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243432

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132726

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:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1456116

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

724138

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:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 11, 2024

The c.3835G>A (p.G1279R) alteration is located in exon 4 (coding exon 3) of the KIAA1683 gene. This alteration results from a G to A substitution at nucleotide position 3835, causing the glycine (G) at amino acid position 1279 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0070

T;T;.;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.45

T;T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.76

.;.;.;N

REVEL

Benign

0.081

Sift

Uncertain

0.021

.;.;.;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.95

.;P;.;.

Vest4

0.14

MutPred

0.30

.;Gain of MoRF binding (P = 0.0122);.;.;

MVP

0.061

MPC

0.21

ClinPred

0.12

GERP RS

-5.3

Varity_R

0.083

gMVP

0.053

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