Variant chr19-18257742-C-T 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.3542G>A(p.Arg1181Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,610,892 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 16 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.51

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=0.0059554875).

BP6

Variant 19-18257742-C-T is Benign according to our data. Variant chr19-18257742-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649576.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCN	NM_001145304.2 linkuse as main transcript	c.3542G>A	p.Arg1181Gln	missense_variant	4/4	ENST00000392413.5	NP_001138776.1	Q9H0B3-4
IQCN	NM_025249.4 linkuse as main transcript	c.2981G>A	p.Arg994Gln	missense_variant	4/4		NP_079525.1	Q9H0B3-1
IQCN	NM_001145305.2 linkuse as main transcript	c.2843G>A	p.Arg948Gln	missense_variant	4/4		NP_001138777.1	Q9H0B3-5A0JP07
IQCN	XM_005260084.2 linkuse as main transcript	c.3542G>A	p.Arg1181Gln	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.3542G>A	p.Arg1181Gln	missense_variant	4/4	1	NM_001145304.2	ENSP00000376213.2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.2981G>A	p.Arg994Gln	missense_variant	4/4	1		ENSP00000470780.1	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.2843G>A	p.Arg948Gln	missense_variant	4/4	2		ENSP00000472912.1	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.4877G>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00275

AC:

674

AN:

244730

Hom.:

AF XY:

0.00295

AC XY:

395

AN XY:

133766

show subpopulations

Gnomad AFR exome

AF:

0.000855

Gnomad AMR exome

AF:

0.00294

Gnomad ASJ exome

AF:

0.00480

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.000560

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00433

GnomAD4 exome

AF:

0.00377

AC:

5499

AN:

1458644

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

2675

AN XY:

725372

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.00418

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000697

Gnomad4 FIN exome

AF:

0.000327

Gnomad4 NFE exome

AF:

0.00444

Gnomad4 OTH exome

AF:

0.00322

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152248

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00361

Hom.:

Bravo

AF:

0.00280

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000931

AC:

ESP6500EA

AF:

0.00333

AC:

ExAC

AF:

0.00258

AC:

311

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00502

EpiControl

AF:

0.00616

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

IQCN: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.070

DANN

Benign

0.96

DEOGEN2

Benign

0.0049

T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.56

T;T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0060

T;T;T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.10

.;.;.;N

REVEL

Benign

0.048

Sift

Benign

0.27

.;.;.;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.65

.;P;.;.

Vest4

0.070

MVP

0.055

MPC

0.21

ClinPred

0.0036

GERP RS

-4.3

Varity_R

0.024

gMVP

0.046

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