16-19788894-A-G

Position:

• chr16-19788894-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153208.3(IQCK):​c.662A>G​(p.Tyr221Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 2)
• Consequence: IQCK NM_153208.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.65

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030279726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCK	NM_153208.3	c.662A>G	p.Tyr221Cys	missense_variant	7/9	ENST00000695302.1	NP_694940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCK	ENST00000695302.1	c.662A>G	p.Tyr221Cys	missense_variant	7/9		NM_153208.3	ENSP00000511791	P1

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251388 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135862

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: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 2

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2024

The c.662A>G (p.Y221C) alteration is located in exon 8 (coding exon 7) of the IQCK gene. This alteration results from a A to G substitution at nucleotide position 662, causing the tyrosine (Y) at amino acid position 221 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	Benign	0.073
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.10
DANN	Benign	0.33
DEOGEN2	Benign	0.0034	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.030	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.11	N;.
REVEL	Benign	0.052
Sift	Benign	0.20	T;.
Sift4G	Benign	0.21	T;T
Polyphen		0.0030	B;.
Vest4		0.20
MutPred		0.33		Loss of phosphorylation at Y221 (P = 0.2333);Loss of phosphorylation at Y221 (P = 0.2333);
MVP		0.19
MPC		0.18
ClinPred		0.076	T
GERP RS		-11
Varity_R		0.047
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs533411801; hg19: chr16-19800216;