chr19-18257524-G-A
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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
NM_001145304.2 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 1.38
Genes affected
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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 |
---|---|---|---|---|---|---|---|
IQCN | NM_001145304.2 | c.3760C>T | p.Arg1254Cys | missense_variant | 4/4 | ENST00000392413.5 | |
IQCN | NM_025249.4 | c.3199C>T | p.Arg1067Cys | missense_variant | 4/4 | ||
IQCN | NM_001145305.2 | c.3061C>T | p.Arg1021Cys | missense_variant | 4/4 | ||
IQCN | XM_005260084.2 | c.3760C>T | p.Arg1254Cys | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQCN | ENST00000392413.5 | c.3760C>T | p.Arg1254Cys | missense_variant | 4/4 | 1 | NM_001145304.2 | A2 | |
IQCN | ENST00000600328.7 | c.3199C>T | p.Arg1067Cys | missense_variant | 4/4 | 1 | P2 | ||
IQCN | ENST00000600359.7 | c.3061C>T | p.Arg1021Cys | missense_variant | 4/4 | 2 | A2 | ||
IQCN | ENST00000599638.2 | n.5095C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152262Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000862 AC: 21AN: 243684Hom.: 0 AF XY: 0.0000977 AC XY: 13AN XY: 133068
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1459174Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 725804
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74398
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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 | May 28, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;.;D
REVEL
Benign
Sift
Pathogenic
.;.;.;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
MVP
MPC
0.85
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at