2-72971602-G-A

Variant summary

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

The NM_144579.3(SFXN5):​c.709C>T​(p.Leu237Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,902 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SFXN5
NM_144579.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39
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]

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=0.23949343).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SFXN5NM_144579.3 linkuse as main transcriptc.709C>T p.Leu237Phe missense_variant 11/14 ENST00000272433.7 NP_653180.1 Q8TD22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SFXN5ENST00000272433.7 linkuse as main transcriptc.709C>T p.Leu237Phe missense_variant 11/141 NM_144579.3 ENSP00000272433.2 Q8TD22

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461706
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727158
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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
Bravo
AF:
0.0000113

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 submitterclinical testingAmbry GeneticsJan 10, 2022The c.709C>T (p.L237F) alteration is located in exon 11 (coding exon 11) of the SFXN5 gene. This alteration results from a C to T substitution at nucleotide position 709, causing the leucine (L) at amino acid position 237 to be replaced by a phenylalanine (F). 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
Benign
0.16
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.063
T
Eigen
Benign
0.0047
Eigen_PC
Benign
0.050
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.070
Sift
Uncertain
0.025
D
Sift4G
Uncertain
0.039
D
Polyphen
0.41
B
Vest4
0.24
MutPred
0.34
Gain of ubiquitination at K242 (P = 0.1162);
MVP
0.28
MPC
0.46
ClinPred
0.82
D
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.092
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1669995703; hg19: chr2-73198731; COSMIC: COSV55587530; COSMIC: COSV55587530; API