9-69037284-A-AAAGAAG

Position:

• chr9-69037284-A-AAAGAAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000144.5(FXN):​c.165+1352_165+1357dup 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 0.25 (2634 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXN	NM_000144.5	c.165+1352_165+1357dup		intron_variant		ENST00000484259.3	NP_000135.2
FXN	NM_181425.3	c.165+1352_165+1357dup		intron_variant			NP_852090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXN	ENST00000484259.3	c.165+1352_165+1357dup		intron_variant		3	NM_000144.5	ENSP00000419243	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 19471 AN: 78316 Hom.: 2634 Cov.: 0

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.249 AC: 19472 AN: 78308 Hom.: 2634 Cov.: 0 AF XY: 0.254 AC XY: 8890 AN XY: 35054

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.278

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;