rs1456280969

Variant names:

• chr9-69035863-C-A
• NM_000144.5:c.81C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-69035863-C-A
• chr9-69035863-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000144.5(FXN):​c.81C>A​(p.Val27Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,345,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: FXN NM_000144.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.354 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXN	NM_000144.5	c.81C>A	p.Val27Val	synonymous_variant	Exon 1 of 5	ENST00000484259.3	NP_000135.2
FXN	NM_181425.3	c.81C>A	p.Val27Val	synonymous_variant	Exon 1 of 5		NP_852090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXN	ENST00000484259.3	c.81C>A	p.Val27Val	synonymous_variant	Exon 1 of 5	3	NM_000144.5	ENSP00000419243.2
ENSG00000285130	ENST00000642889.1	c.81C>A	p.Val27Val	synonymous_variant	Exon 1 of 25			ENSP00000493780.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1345166 Hom.: 0 Cov.: 36 AF XY: 0.00000151 AC XY: 1 AN XY: 663074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.41e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.8
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-71650779;