9-69037284-AAAGAAGAAGAAGAAG-AAAGAAGAAGAAGAAGAAGAAGAAGAAG

Position:

• chr9-69037284-AAAGAAGAAGAAGAAG-AAAGAAGAAGAAGAAGAAGAAGAAGAAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000144.5(FXN):​c.165+1346_165+1357dupGAAGAAGAAGAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0015 (3 hom., cov: 0)
• Consequence: FXN NM_000144.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327

Genes affected

FXN (HGNC:3951): (frataxin) This nuclear gene encodes a mitochondrial protein which belongs to the FRATAXIN family. The protein functions in regulating mitochondrial iron transport and respiration. The expansion of intronic trinucleotide repeat GAA from 8-33 repeats to >90 repeats results in Friedreich ataxia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ENSG00000285130 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00147 (115/78054) while in subpopulation SAS AF= 0.00857 (19/2216). AF 95% confidence interval is 0.00561. There are 3 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXN	NM_000144.5	c.165+1346_165+1357dupGAAGAAGAAGAA		intron_variant		ENST00000484259.3	NP_000135.2
FXN	NM_181425.3	c.165+1346_165+1357dupGAAGAAGAAGAA		intron_variant			NP_852090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXN	ENST00000484259.3	c.165+1346_165+1357dupGAAGAAGAAGAA		intron_variant		3	NM_000144.5	ENSP00000419243.2
ENSG00000285130	ENST00000642889.1	c.165+1346_165+1357dupGAAGAAGAAGAA		intron_variant				ENSP00000493780.1

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 115 AN: 78062 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.000710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00487

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00248

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00625

Gnomad NFE AF: 0.000886

Gnomad OTH AF: 0.00415

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

GnomAD4 genome AF: 0.00147 AC: 115 AN: 78054 Hom.: 3 Cov.: 0 AF XY: 0.00175 AC XY: 61 AN XY: 34948

Gnomad4 AFR AF: 0.000709

Gnomad4 AMR AF: 0.00486

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00248

Gnomad4 SAS AF: 0.00857

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000886

Gnomad4 OTH AF: 0.00416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs193922938; hg19: chr9-71652200;