rs10512174

Positions:

• chr9-86271659-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030940.4(ISCA1):​c.241+348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,980 control chromosomes in the GnomAD database, including 15,248 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15248 hom., cov: 32)
• Consequence: ISCA1 NM_030940.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISCA1	NM_030940.4	c.241+348G>A		intron_variant		ENST00000375991.9	NP_112202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISCA1	ENST00000375991.9	c.241+348G>A		intron_variant		1	NM_030940.4	ENSP00000365159	P1
ISCA1	ENST00000311534.6	c.-54+348G>A		intron_variant		2		ENSP00000339003
ISCA1	ENST00000326094.4	c.241+348G>A		intron_variant		3		ENSP00000365157
ISCA1	ENST00000637705.1	c.178+348G>A		intron_variant		5		ENSP00000489740

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67604 AN: 151864 Hom.: 15225 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67673 AN: 151980 Hom.: 15248 Cov.: 32 AF XY: 0.440 AC XY: 32656 AN XY: 74262

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.492

Alfa AF: 0.441 Hom.: 7063

Bravo AF: 0.456

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.10
DANN	Benign	0.42

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: rs10512174; hg19: chr9-88886574;