2-69400705-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001002755.4(NFU1):c.546-168_546-167insA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (14385 hom., cov: 0)
• Consequence: NFU1 NM_001002755.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970

Genes affected

NFU1 (HGNC:16287): (NFU1 iron-sulfur cluster scaffold) This gene encodes a protein that is localized to mitochondria and plays a critical role in iron-sulfur cluster biogenesis. The encoded protein assembles and transfers 4Fe-4S clusters to target apoproteins including succinate dehydrogenase and lipoic acid synthase. Mutations in this gene are a cause of multiple mitochondrial dysfunctions syndrome-1, and pseudogenes of this gene are located on the short arms of chromosomes 1 and 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-69400705-A-AT is Benign according to our data. Variant chr2-69400705-A-AT is described in ClinVar as [Benign]. Clinvar id is 1233202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFU1	NM_001002755.4	c.546-168_546-167insA		intron_variant		ENST00000410022.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFU1	ENST00000410022.7	c.546-168_546-167insA		intron_variant		1	NM_001002755.4	A1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 65569 AN: 149808 Hom.: 14373 Cov.: 0

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.438 AC: 65606 AN: 149892 Hom.: 14385 Cov.: 0 AF XY: 0.435 AC XY: 31816 AN XY: 73096

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.444

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs61684281; hg19: chr2-69627837;