16-19718398-C-T

Variant names:

• chr16-19718398-C-T
• rs1382333493
• NM_153208.3:c.92C>T

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.92C>T​(p.Thr31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,453,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.000010 (0 hom.)
• Consequence: IQCK NM_153208.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.249
• 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=0.07108015).

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.92C>T	p.Thr31Ile	missense	Exon 1 of 9	NP_694940.1	Q8N0W5-1
	IQCK	NM_001394804.1		c.92C>T	p.Thr31Ile	missense	Exon 1 of 10	NP_001381733.1	Q8N0W5-1
	IQCK	NM_001394806.1		c.92C>T	p.Thr31Ile	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.92C>T	p.Thr31Ile	missense	Exon 1 of 9	ENSP00000511791.1	Q8N0W5-1
	IQCK	ENST00000320394.10	TSL:1	c.92C>T	p.Thr31Ile	missense	Exon 2 of 10	ENSP00000324901.6	Q8N0W5-1
	IQCK	ENST00000308214.13	TSL:1	n.92C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000309261.9	Q8N0W5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1453926 Hom.: 0 Cov.: 31 AF XY: 0.0000166 AC XY: 12 AN XY: 722512

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 43308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.00 AC: 0 AN: 84500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1109264

Other (OTH) AF: 0.00 AC: 0 AN: 60072

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	3.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.25
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.014
Sift	Benign	0.17	T
Sift4G	Benign	0.47	T
Polyphen		0.026	B
Vest4		0.022
MutPred		0.39		Loss of glycosylation at T31 (P = 0.003)
MVP		0.27
MPC		0.15
ClinPred		0.27	T
GERP RS		-0.0090
PromoterAI		0.013	Neutral
Varity_R		0.040
gMVP		0.19
Mutation Taster		=97/3	polymorphism

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: rs1382333493; hg19: chr16-19729720;