Variant chr9-69035879-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000144.5(FXN):c.97T>G(p.Leu33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,469,842 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

FXN
NM_000144.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.09

Variant links:

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 links:

ENSG00000285130 (HGNC:):

ENSG00000285130 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07563773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXN	NM_000144.5 linkuse as main transcript	c.97T>G	p.Leu33Val	missense_variant	1/5	ENST00000484259.3	NP_000135.2	Q16595-1A0A0S2Z3G4
FXN	NM_181425.3 linkuse as main transcript	c.97T>G	p.Leu33Val	missense_variant	1/5		NP_852090.1	Q16595-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXN	ENST00000484259.3 linkuse as main transcript	c.97T>G	p.Leu33Val	missense_variant	1/5	3	NM_000144.5	ENSP00000419243.2		Q16595-1
ENSG00000285130	ENST00000642889.1 linkuse as main transcript	c.97T>G	p.Leu33Val	missense_variant	1/25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000314

AC:

AN:

95482

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

53530

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000853

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1319974

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

651138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000326

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:

0.0000191

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149868

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73208

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000264

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.53

DANN

Benign

0.55

DEOGEN2

Benign

0.33

T;.;.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.51

.;T;T;T;T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.076

T;T;T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.4

L;L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.52

.;N;N;.;.;.

REVEL

Benign

0.24

Sift

Benign

0.31

.;T;T;.;.;.

Sift4G

Benign

0.85

.;T;T;.;.;.

Polyphen

0.038

B;B;.;B;.;.

Vest4

0.061, 0.10

MutPred

0.14

Gain of MoRF binding (P = 0.0924);Gain of MoRF binding (P = 0.0924);Gain of MoRF binding (P = 0.0924);Gain of MoRF binding (P = 0.0924);Gain of MoRF binding (P = 0.0924);Gain of MoRF binding (P = 0.0924);

MVP

0.58

ClinPred

0.083

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.056

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over