chr19-18257773-G-T

Position:

• chr19-18257773-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001145304.2(IQCN):​c.3511C>A​(p.Arg1171Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: IQCN NM_001145304.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.788

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCN	NM_001145304.2	c.3511C>A	p.Arg1171Ser	missense_variant	4/4	ENST00000392413.5
IQCN	NM_025249.4	c.2950C>A	p.Arg984Ser	missense_variant	4/4
IQCN	NM_001145305.2	c.2812C>A	p.Arg938Ser	missense_variant	4/4
IQCN	XM_005260084.2	c.3511C>A	p.Arg1171Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCN	ENST00000392413.5	c.3511C>A	p.Arg1171Ser	missense_variant	4/4	1	NM_001145304.2	A2
IQCN	ENST00000600328.7	c.2950C>A	p.Arg984Ser	missense_variant	4/4	1		P2
IQCN	ENST00000600359.7	c.2812C>A	p.Arg938Ser	missense_variant	4/4	2		A2
IQCN	ENST00000599638.2	n.4846C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458768 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

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

Feb 17, 2024

The c.3511C>A (p.R1171S) 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 3511, causing the arginine (R) at amino acid position 1171 to be replaced by a serine (S). 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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Uncertain	-0.12	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.82
MutPred		0.62		.;Gain of glycosylation at R984 (P = 0.0412);.;.;
MVP		0.64
MPC		0.77
ClinPred		0.98	D
GERP RS		1.8
Varity_R		0.41
gMVP		0.69

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: chr19-18368583;