chr19-18257359-A-G

Position:

• chr19-18257359-A-G

Variant summary

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

The NM_001145304.2(IQCN):​c.3925T>C​(p.Ser1309Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IQCN NM_001145304.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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=0.30397868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCN	NM_001145304.2	c.3925T>C	p.Ser1309Pro	missense_variant	4/4	ENST00000392413.5
IQCN	NM_025249.4	c.3364T>C	p.Ser1122Pro	missense_variant	4/4
IQCN	NM_001145305.2	c.3226T>C	p.Ser1076Pro	missense_variant	4/4
IQCN	XM_005260084.2	c.3925T>C	p.Ser1309Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCN	ENST00000392413.5	c.3925T>C	p.Ser1309Pro	missense_variant	4/4	1	NM_001145304.2	A2
IQCN	ENST00000600328.7	c.3364T>C	p.Ser1122Pro	missense_variant	4/4	1		P2
IQCN	ENST00000600359.7	c.3226T>C	p.Ser1076Pro	missense_variant	4/4	2		A2
IQCN	ENST00000599638.2	n.5260T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249360 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460096 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	-0.083
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.54	T;T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.98	.;D;.;.
Vest4		0.37
MutPred		0.54		.;Gain of catalytic residue at S1122 (P = 0.009);.;.;
MVP		0.30
MPC		0.80
ClinPred		0.77	D
GERP RS		0.91
Varity_R		0.24
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs763112620; hg19: chr19-18368169;