Variant chr9-69035823-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000144.5(FXN):c.41C>A(p.Ala14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000357 in 1,512,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

FXN
NM_000144.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.109

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006406367).

BP6

Variant 9-69035823-C-A is Benign according to our data. Variant chr9-69035823-C-A is described in ClinVar as [Benign]. Clinvar id is 804821.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXN	NM_000144.5 linkuse as main transcript	c.41C>A	p.Ala14Glu	missense_variant	1/5	ENST00000484259.3
FXN	NM_181425.3 linkuse as main transcript	c.41C>A	p.Ala14Glu	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXN	ENST00000484259.3 linkuse as main transcript	c.41C>A	p.Ala14Glu	missense_variant	1/5	3	NM_000144.5	P1	Q16595-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

109614

Hom.:

AF XY:

0.000198

AC XY:

AN XY:

60732

show subpopulations

Gnomad AFR exome

AF:

0.000367

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00199

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1360262

Hom.:

Cov.:

AF XY:

0.0000238

AC XY:

AN XY:

670880

show subpopulations

Gnomad4 AFR exome

AF:

0.000105

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000746

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000176

GnomAD4 genome

AF:

0.000105

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000869

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000383

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.30

T;.;.;T;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.46

.;T;T;T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0064

T;T;T;T;T;T

MetaSVM

Uncertain

0.011

MutationAssessor

Benign

1.1

L;L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.48

.;N;N;.;.;.

REVEL

Benign

0.27

Sift

Uncertain

0.016

.;D;T;.;.;.

Sift4G

Benign

0.11

.;T;T;.;.;.

Polyphen

0.20

B;P;.;B;.;.

Vest4

0.088, 0.19

MutPred

0.20

Loss of MoRF binding (P = 0.0632);Loss of MoRF binding (P = 0.0632);Loss of MoRF binding (P = 0.0632);Loss of MoRF binding (P = 0.0632);Loss of MoRF binding (P = 0.0632);Loss of MoRF binding (P = 0.0632);

MVP

0.49

ClinPred

0.027

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.099

gMVP

0.21

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