rs10512174

Variant names:

• chr9-86271659-C-T
• rs10512174
• NM_030940.4:c.241+348G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• multiple mitochondrial dysfunctions syndrome 5

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ISCA1	NM_030940.4	c.241+348G>A		intron_variant	Intron 3 of 3	ENST00000375991.9	NP_112202.2

Ensembl

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

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

African (AFR) AF: 0.459 AC: 19001 AN: 41430

American (AMR) AF: 0.460 AC: 7022 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1898 AN: 3470

East Asian (EAS) AF: 0.502 AC: 2598 AN: 5174

South Asian (SAS) AF: 0.469 AC: 2261 AN: 4818

European-Finnish (FIN) AF: 0.359 AC: 3780 AN: 10530

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29505 AN: 67982

Other (OTH) AF: 0.492 AC: 1038 AN: 2110

Alfa AF: 0.442 Hom.: 7922

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
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10512174; hg19: chr9-88886574;