16-19718355-A-C

Variant names:

• chr16-19718355-A-C
• NM_153208.3:c.49A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153208.3(IQCK):​c.49A>C​(p.Ser17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IQCK NM_153208.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16

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

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=0.08822706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCK	NM_153208.3	c.49A>C	p.Ser17Arg	missense_variant	Exon 1 of 9	ENST00000695302.1	NP_694940.1
KNOP1	NM_001012991.3	c.-200T>G		upstream_gene_variant		ENST00000219837.12	NP_001013009.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCK	ENST00000695302.1	c.49A>C	p.Ser17Arg	missense_variant	Exon 1 of 9		NM_153208.3	ENSP00000511791.1
KNOP1	ENST00000219837.12	c.-200T>G		upstream_gene_variant		1	NM_001012991.3	ENSP00000219837.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458022 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.49A>C (p.S17R) alteration is located in exon 2 (coding exon 1) of the IQCK gene. This alteration results from a A to C substitution at nucleotide position 49, causing the serine (S) at amino acid position 17 to be replaced by an arginine (R). 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	0.22
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.89	N;.
REVEL	Benign	0.11
Sift	Benign	0.043	D;.
Sift4G	Benign	0.15	T;T
Polyphen		0.22	B;.
Vest4		0.11
MutPred		0.18		Gain of MoRF binding (P = 0.0078);Gain of MoRF binding (P = 0.0078);
MVP		0.31
MPC		0.26
ClinPred		0.64	D
GERP RS		-6.5
Varity_R		0.20
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-19729677;