9-69037284-AAAGAAGAAGAAGAAG-AAAGAAGAAGAAGAAGAAGAAGAAG

Variant names:

• chr9-69037284-A-AAAGAAGAAG
• rs193922938
• NM_000144.5:c.165+1349_165+1357dupGAAGAAGAA

Variant summary

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

The NM_000144.5(FXN):​c.165+1349_165+1357dupGAAGAAGAA 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 0.11 (750 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.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXN	NM_000144.5	c.165+1349_165+1357dupGAAGAAGAA		intron_variant	Intron 1 of 4	ENST00000484259.3	NP_000135.2
FXN	NM_181425.3	c.165+1349_165+1357dupGAAGAAGAA		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+1338insAAGAAGAAG		intron_variant	Intron 1 of 4	3	NM_000144.5	ENSP00000419243.2
ENSG00000285130	ENST00000642889.1	c.165+1337_165+1338insAAGAAGAAG		intron_variant	Intron 1 of 24			ENSP00000493780.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 8608 AN: 77994 Hom.: 753 Cov.: 0

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.110 AC: 8612 AN: 77990 Hom.: 750 Cov.: 0 AF XY: 0.114 AC XY: 3972 AN XY: 34908

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0612

Gnomad4 NFE AF: 0.0697

Gnomad4 OTH AF: 0.116

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;