19-18257796-G-T

Position:

• chr19-18257796-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145304.2(IQCN):​c.3488C>A​(p.Thr1163Asn) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IQCN NM_001145304.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

Genes affected

IQCN (HGNC:29350): (IQ motif containing N) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3454801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCN	NM_001145304.2	c.3488C>A	p.Thr1163Asn	missense_variant	4/4	ENST00000392413.5
IQCN	NM_025249.4	c.2927C>A	p.Thr976Asn	missense_variant	4/4
IQCN	NM_001145305.2	c.2789C>A	p.Thr930Asn	missense_variant	4/4
IQCN	XM_005260084.2	c.3488C>A	p.Thr1163Asn	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCN	ENST00000392413.5	c.3488C>A	p.Thr1163Asn	missense_variant	4/4	1	NM_001145304.2	A2
IQCN	ENST00000600328.7	c.2927C>A	p.Thr976Asn	missense_variant	4/4	1		P2
IQCN	ENST00000600359.7	c.2789C>A	p.Thr930Asn	missense_variant	4/4	2		A2
IQCN	ENST00000599638.2	n.4823C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 01, 2021

The c.3488C>A (p.T1163N) alteration is located in exon 4 (coding exon 3) of the KIAA1683 gene. This alteration results from a C to A substitution at nucleotide position 3488, causing the threonine (T) at amino acid position 1163 to be replaced by an asparagine (N). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T;T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		0.98	.;D;.;.
Vest4		0.48
MutPred		0.57		.;Loss of catalytic residue at T976 (P = 0.0869);.;.;
MVP		0.30
MPC		0.57
ClinPred		0.55	D
GERP RS		3.3
Varity_R		0.093
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-18368606;