9-69037284-AAAGAAGAAGAAGAAG-AAAGAAGAAGAAGAAGAAGAAG

Variant names:

• chr9-69037284-A-AAAGAAG
• rs193922938
• NM_000144.5:c.165+1352_165+1357dupGAAGAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000144.5(FXN):​c.165+1352_165+1357dupGAAGAA 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
• Publications: 0 publications found

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]

FXN Gene-Disease associations (from GenCC):

• Friedreich ataxia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Friedreich ataxia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Friedreich ataxia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FXN	NM_000144.5	c.165+1352_165+1357dupGAAGAA		intron_variant	Intron 1 of 4	ENST00000484259.3	NP_000135.2
FXN	NM_181425.3	c.165+1352_165+1357dupGAAGAA		intron_variant	Intron 1 of 4		NP_852090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXN	ENST00000484259.3	c.165+1337_165+1338insAAGAAG		intron_variant	Intron 1 of 4	3	NM_000144.5	ENSP00000419243.2
ENSG00000285130	ENST00000642889.1	c.165+1337_165+1338insAAGAAG		intron_variant	Intron 1 of 24			ENSP00000493780.1

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

African (AFR) AF: 0.219 AC: 4634 AN: 21174

American (AMR) AF: 0.219 AC: 1485 AN: 6796

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 653 AN: 2192

East Asian (EAS) AF: 0.247 AC: 794 AN: 3220

South Asian (SAS) AF: 0.394 AC: 873 AN: 2218

European-Finnish (FIN) AF: 0.255 AC: 340 AN: 1332

Middle Eastern (MID) AF: 0.359 AC: 51 AN: 142

European-Non Finnish (NFE) AF: 0.255 AC: 10122 AN: 39712

Other (OTH) AF: 0.278 AC: 267 AN: 962

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs193922938; hg19: chr9-71652200;