chr19-18257524-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145304.2(IQCN):​c.3760C>T​(p.Arg1254Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,611,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

2
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
Variant links:
Genes affected
IQCN (HGNC:29350): (IQ motif containing N) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IQCNNM_001145304.2 linkuse as main transcriptc.3760C>T p.Arg1254Cys missense_variant 4/4 ENST00000392413.5
IQCNNM_025249.4 linkuse as main transcriptc.3199C>T p.Arg1067Cys missense_variant 4/4
IQCNNM_001145305.2 linkuse as main transcriptc.3061C>T p.Arg1021Cys missense_variant 4/4
IQCNXM_005260084.2 linkuse as main transcriptc.3760C>T p.Arg1254Cys missense_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IQCNENST00000392413.5 linkuse as main transcriptc.3760C>T p.Arg1254Cys missense_variant 4/41 NM_001145304.2 A2Q9H0B3-4
IQCNENST00000600328.7 linkuse as main transcriptc.3199C>T p.Arg1067Cys missense_variant 4/41 P2Q9H0B3-1
IQCNENST00000600359.7 linkuse as main transcriptc.3061C>T p.Arg1021Cys missense_variant 4/42 A2Q9H0B3-5
IQCNENST00000599638.2 linkuse as main transcriptn.5095C>T non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.000223
AC:
34
AN:
152262
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000820
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000862
AC:
21
AN:
243684
Hom.:
0
AF XY:
0.0000977
AC XY:
13
AN XY:
133068
show subpopulations
Gnomad AFR exome
AF:
0.000781
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000110
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000920
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1459174
Hom.:
0
Cov.:
30
AF XY:
0.0000358
AC XY:
26
AN XY:
725804
show subpopulations
Gnomad4 AFR exome
AF:
0.000837
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000223
AC:
34
AN:
152262
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.000820
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000850
Hom.:
0
Bravo
AF:
0.000246
ESP6500AA
AF:
0.00114
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000413
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

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 submitterclinical testingAmbry GeneticsMay 28, 2023The c.3760C>T (p.R1254C) 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 3760, causing the arginine (R) at amino acid position 1254 to be replaced by a cysteine (C). 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T;.;.
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.071
D
MetaRNN
Uncertain
0.43
T;T;T;T
MetaSVM
Benign
-1.2
T
MutationTaster
Benign
0.81
D;N;N
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.6
.;.;.;D
REVEL
Benign
0.13
Sift
Pathogenic
0.0
.;.;.;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.58
MVP
0.21
MPC
0.85
ClinPred
0.30
T
GERP RS
3.3
Varity_R
0.28
gMVP
0.39

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.

Other links and lift over

dbSNP: rs139912303; hg19: chr19-18368334; COSMIC: COSV62748193; COSMIC: COSV62748193; API