Variant rs880844 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001320042.1(ISCU):c.*888G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,391,868 control chromosomes in the GnomAD database, including 47,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3870 hom., cov: 32)

Exomes 𝑓: 0.26 ( 43395 hom. )

Consequence

ISCU
NM_001320042.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.198

Variant links:

Genes affected

ISCU (HGNC:29882): (iron-sulfur cluster assembly enzyme) This gene encodes a component of the iron-sulfur (Fe-S) cluster scaffold. Fe-S clusters are cofactors that play a role in the function of a diverse set of enzymes, including those that regulate metabolism, iron homeostasis, and oxidative stress response. Alternative splicing results in transcript variants encoding different protein isoforms that localize either to the cytosol or to the mitochondrion. Mutations in this gene have been found in patients with hereditary myopathy with lactic acidosis. A disease-associated mutation in an intron may activate a cryptic splice site, resulting in the production of a splice variant encoding a putatively non-functional protein. A pseudogene of this gene is present on chromosome 1. [provided by RefSeq, Feb 2016]

ISCU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-108568592-G-A is Benign according to our data. Variant chr12-108568592-G-A is described in ClinVar as [Benign]. Clinvar id is 681977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISCU	NM_213595.4 link	c.419-239G>A		intron_variant	Intron 4 of 4	ENST00000311893.14	NP_998760.1	Q9H1K1-1B3KQ30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISCU	ENST00000311893.14 link	c.419-239G>A		intron_variant	Intron 4 of 4	1	NM_213595.4	ENSP00000310623.9		Q9H1K1-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30283

AN:

152064

Hom.:

3870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.258

AC:

319501

AN:

1239686

Hom.:

43395

Cov.:

AF XY:

0.261

AC XY:

156373

AN XY:

600028

show subpopulations

Gnomad4 AFR exome

AF:

0.0393

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.336

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.199

AC:

30283

AN:

152182

Hom.:

3870

Cov.:

AF XY:

0.205

AC XY:

15273

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0472

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.493

Gnomad4 SAS

AF:

0.359

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.239

Hom.:

2102

Bravo

AF:

0.184

Asia WGS

AF:

0.400

AC:

1389

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.61

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