16-19733786-C-A

Variant names:

• chr16-19733786-C-A
• NM_153208.3:c.335C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153208.3(IQCK):​c.335C>A​(p.Pro112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IQCK NM_153208.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41914463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCK	NM_153208.3	MANE Select	c.335C>A	p.Pro112His	missense	Exon 3 of 9	NP_694940.1	Q8N0W5-1
	IQCK	NM_001394804.1		c.335C>A	p.Pro112His	missense	Exon 3 of 10	NP_001381733.1	Q8N0W5-1
	IQCK	NM_001394806.1		c.335C>A	p.Pro112His	missense	Exon 3 of 8	NP_001381735.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCK	ENST00000695302.1	MANE Select	c.335C>A	p.Pro112His	missense	Exon 3 of 9	ENSP00000511791.1	Q8N0W5-1
	IQCK	ENST00000320394.10	TSL:1	c.335C>A	p.Pro112His	missense	Exon 4 of 10	ENSP00000324901.6	Q8N0W5-1
	IQCK	ENST00000308214.13	TSL:1	n.335C>A		non_coding_transcript_exon	Exon 4 of 8	ENSP00000309261.9	Q8N0W5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.2
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.10
Sift	Benign	0.084	T
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.30		Gain of sheet (P = 0.0827)
MVP		0.38
MPC		0.66
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.21
gMVP		0.34

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

Other links and lift over

hg19: chr16-19745108;