Variant chr19-18257391-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001145304.2(IQCN):c.3893A>G(p.His1298Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,611,126 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.05

Variant links:

Genes affected

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

IQCN links:

IQCN (HGNC:):

IQCN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008956045).

BP6

Variant 19-18257391-T-C is Benign according to our data. Variant chr19-18257391-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3110570.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCN	NM_001145304.2 linkuse as main transcript	c.3893A>G	p.His1298Arg	missense_variant	4/4	ENST00000392413.5	NP_001138776.1	Q9H0B3-4
IQCN	NM_025249.4 linkuse as main transcript	c.3332A>G	p.His1111Arg	missense_variant	4/4		NP_079525.1	Q9H0B3-1
IQCN	NM_001145305.2 linkuse as main transcript	c.3194A>G	p.His1065Arg	missense_variant	4/4		NP_001138777.1	Q9H0B3-5A0JP07
IQCN	XM_005260084.2 linkuse as main transcript	c.3893A>G	p.His1298Arg	missense_variant	4/4		XP_005260141.1	Q9H0B3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IQCN	ENST00000392413.5 linkuse as main transcript	c.3893A>G	p.His1298Arg	missense_variant	4/4	1	NM_001145304.2	ENSP00000376213.2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.3332A>G	p.His1111Arg	missense_variant	4/4	1		ENSP00000470780.1	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.3194A>G	p.His1065Arg	missense_variant	4/4	2		ENSP00000472912.1	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.5228A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.000802

AC:

122

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000630

AC:

156

AN:

247484

Hom.:

AF XY:

0.000654

AC XY:

AN XY:

134488

show subpopulations

Gnomad AFR exome

AF:

0.000374

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000986

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.00120

AC:

1755

AN:

1458822

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

830

AN XY:

725716

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000588

Gnomad4 NFE exome

AF:

0.00146

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.000801

AC:

122

AN:

152304

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000876

Hom.:

Bravo

AF:

0.00103

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000651

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.000949

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0040

DANN

Benign

0.15

DEOGEN2

Benign

0.0099

T;T;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.43

T;T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0090

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

.;.;.;N

REVEL

Benign

0.040

Sift

Benign

0.35

.;.;.;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0010

.;B;.;.

Vest4

0.11

MVP

0.17

MPC

0.23

ClinPred

0.018

GERP RS

-9.3

Varity_R

0.028

gMVP

0.062

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over