chr16-19730493-C-A

Variant summary

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

The NM_153208.3(IQCK):​c.245C>A​(p.Thr82Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T82M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IQCK
NM_153208.3 missense, splice_region

Scores

19
Splicing: ADA: 0.0005339
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0870
Variant links:
Genes affected
IQCK (HGNC:28556): (IQ motif containing K) This gene belongs to the IQ motif-containing family of proteins. The IQ motif serves as a binding site for different EF-hand proteins such as calmodulin. This gene was identified as a potential candidate gene for obsessive-compulsive disorder in a genome-wide association study. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

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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=0.111888945).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IQCKNM_153208.3 linkc.245C>A p.Thr82Lys missense_variant, splice_region_variant Exon 2 of 9 ENST00000695302.1 NP_694940.1 Q8N0W5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IQCKENST00000695302.1 linkc.245C>A p.Thr82Lys missense_variant, splice_region_variant Exon 2 of 9 NM_153208.3 ENSP00000511791.1 Q8N0W5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452688
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
722588
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:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
9.8
DANN
Benign
0.89
DEOGEN2
Benign
0.0039
T;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.9
N;.
REVEL
Benign
0.031
Sift
Benign
0.28
T;.
Sift4G
Benign
0.12
T;T
Polyphen
0.65
P;.
Vest4
0.25
MutPred
0.41
Gain of methylation at T82 (P = 0.004);Gain of methylation at T82 (P = 0.004);
MVP
0.22
MPC
0.56
ClinPred
0.20
T
GERP RS
2.5
Varity_R
0.10
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00053
dbscSNV1_RF
Benign
0.11
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-19741815; API