Variant chr9-86266085-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_030940.4(ISCA1):c.348C>T(p.Asn116=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0237 in 1,612,782 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 53 hom., cov: 32)

Exomes 𝑓: 0.024 ( 517 hom. )

Consequence

ISCA1
NM_030940.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.64

Variant links:

Genes affected

ISCA1 (HGNC:28660): (iron-sulfur cluster assembly 1) ISCA1 is a mitochondrial protein involved in the biogenesis and assembly of iron-sulfur clusters, which play a role in electron-transfer reactions (Cozar-Castellano et al., 2004 [PubMed 15262227]).[supplied by OMIM, Mar 2008]

ISCA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 9-86266085-G-A is Benign according to our data. Variant chr9-86266085-G-A is described in ClinVar as [Benign]. Clinvar id is 1169189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.018 (2738/152296) while in subpopulation NFE AF= 0.0259 (1764/68014). AF 95% confidence interval is 0.0249. There are 53 homozygotes in gnomad4. There are 1239 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISCA1	NM_030940.4 linkuse as main transcript	c.348C>T	p.Asn116=	synonymous_variant	4/4	ENST00000375991.9	NP_112202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISCA1	ENST00000375991.9 linkuse as main transcript	c.348C>T	p.Asn116=	synonymous_variant	4/4	1	NM_030940.4	ENSP00000365159	P1	Q9BUE6-1
ISCA1	ENST00000311534.6 linkuse as main transcript	c.54C>T	p.Asn18=	synonymous_variant	4/4	2		ENSP00000339003
ISCA1	ENST00000637705.1 linkuse as main transcript			downstream_gene_variant		5		ENSP00000489740

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2735

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00574

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0193

AC:

4742

AN:

245338

Hom.:

AF XY:

0.0197

AC XY:

2623

AN XY:

132934

show subpopulations

Gnomad AFR exome

AF:

0.00490

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0791

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00814

Gnomad FIN exome

AF:

0.00386

Gnomad NFE exome

AF:

0.0263

Gnomad OTH exome

AF:

0.0236

GnomAD4 exome

AF:

0.0243

AC:

35453

AN:

1460486

Hom.:

517

Cov.:

AF XY:

0.0241

AC XY:

17528

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.0166

Gnomad4 ASJ exome

AF:

0.0791

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00877

Gnomad4 FIN exome

AF:

0.00408

Gnomad4 NFE exome

AF:

0.0266

Gnomad4 OTH exome

AF:

0.0283

GnomAD4 genome

AF:

0.0180

AC:

2738

AN:

152296

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1239

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00573

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.0859

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0327

Alfa

AF:

0.0303

Hom.:

Bravo

AF:

0.0198

EpiCase

AF:

0.0325

EpiControl

AF:

0.0297

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.4

DANN

Benign

0.83

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