NM_153208.3:c.11C>G

Variant names:

• chr16-19718317-C-G
• rs907587880
• NM_153208.3:c.11C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153208.3(IQCK):​c.11C>G​(p.Pro4Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. 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. P4L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IQCK NM_153208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• 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]

KNOP1 (HGNC:34404): (lysine rich nucleolar protein 1) The protein encoded by this gene is a nucleolar protein that interacts with zinc finger 106 protein. The encoded protein has several of the same characteristics as nucleostemin and may be involved in testis development. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13733324).

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.11C>G	p.Pro4Arg	missense	Exon 1 of 9	NP_694940.1	Q8N0W5-1
	IQCK	NM_001394804.1		c.11C>G	p.Pro4Arg	missense	Exon 1 of 10	NP_001381733.1	Q8N0W5-1
	IQCK	NM_001394806.1		c.11C>G	p.Pro4Arg	missense	Exon 1 of 8	NP_001381735.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCK	ENST00000695302.1	MANE Select	c.11C>G	p.Pro4Arg	missense	Exon 1 of 9	ENSP00000511791.1	Q8N0W5-1
	IQCK	ENST00000320394.10	TSL:1	c.11C>G	p.Pro4Arg	missense	Exon 2 of 10	ENSP00000324901.6	Q8N0W5-1
	IQCK	ENST00000308214.13	TSL:1	n.11C>G		non_coding_transcript_exon	Exon 2 of 8	ENSP00000309261.9	Q8N0W5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.71
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.052
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.12
MutPred		0.44		Gain of MoRF binding (P = 2e-04)
MVP		0.46
MPC		0.47
ClinPred		0.87	D
GERP RS		-0.61
PromoterAI		0.029	Neutral
Varity_R		0.067
gMVP		0.32

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

dbSNP: rs907587880; hg19: chr16-19729639;