Variant 2-73000445-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_144579.3(SFXN5):c.454C>T(p.Arg152Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000115 in 1,559,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SFXN5
NM_144579.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

Variant links:

Genes affected

SFXN5 (HGNC:16073): (sideroflexin 5) Predicted to enable citrate transmembrane transporter activity. Predicted to be involved in citrate transport and mitochondrial transmembrane transport. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SFXN5 links:

SFXN5 (HGNC:):

SFXN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN5	NM_144579.3 linkuse as main transcript	c.454C>T	p.Arg152Cys	missense_variant	8/14	ENST00000272433.7	NP_653180.1	Q8TD22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN5	ENST00000272433.7 linkuse as main transcript	c.454C>T	p.Arg152Cys	missense_variant	8/14	1	NM_144579.3	ENSP00000272433.2		Q8TD22

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000236

AC:

AN:

169736

Hom.:

AF XY:

0.0000335

AC XY:

AN XY:

89516

show subpopulations

Gnomad AFR exome

AF:

0.0000978

Gnomad AMR exome

AF:

0.0000778

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:

0.0000147

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1407108

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

694528

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.0000546

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000924

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000869

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.454C>T (p.R152C) alteration is located in exon 8 (coding exon 8) of the SFXN5 gene. This alteration results from a C to T substitution at nucleotide position 454, causing the arginine (R) at amino acid position 152 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.43

T;T;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

-0.056

MutationAssessor

Pathogenic

3.7

H;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.7

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0040

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.95

MVP

0.54

MPC

1.2

ClinPred

0.99

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.91

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