Variant 16-19735353-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_153208.3(IQCK):c.377G>T(p.Cys126Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,459,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IQCK
NM_153208.3 missense, splice_region

Scores

Splicing: ADA: 0.9991

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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]

IQCK links:

IQCK (HGNC:):

IQCK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCK	NM_153208.3 linkuse as main transcript	c.377G>T	p.Cys126Phe	missense_variant, splice_region_variant	4/9	ENST00000695302.1	NP_694940.1	Q8N0W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCK	ENST00000695302.1 linkuse as main transcript	c.377G>T	p.Cys126Phe	missense_variant, splice_region_variant	4/9		NM_153208.3	ENSP00000511791.1		Q8N0W5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251260

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

6.85e-7

AC:

AN:

1459208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000741

Hom.:

Bravo

AF:

0.00000756

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

Jul 19, 2023

The c.377G>T (p.C126F) alteration is located in exon 5 (coding exon 4) of the IQCK gene. This alteration results from a G to T substitution at nucleotide position 377, causing the cysteine (C) at amino acid position 126 to be replaced by a phenylalanine (F). 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

0.44

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-9.7

D;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.70

MVP

0.62

MPC

0.78

ClinPred

1.0

GERP RS

5.2

Varity_R

0.91

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.86

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: 0

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