10-101038643-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030971.6(SFXN3):​c.772C>T​(p.Arg258Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

SFXN3
NM_030971.6 missense, splice_region

Scores

1
5
11
Splicing: ADA: 0.01675
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.999
Variant links:
Genes affected
SFXN3 (HGNC:16087): (sideroflexin 3) Enables serine transmembrane transporter activity. Involved in serine import into mitochondrion. 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36407563).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SFXN3NM_030971.6 linkc.772C>T p.Arg258Cys missense_variant, splice_region_variant Exon 10 of 12 ENST00000393459.6 NP_112233.3 Q9BWM7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SFXN3ENST00000393459.6 linkc.772C>T p.Arg258Cys missense_variant, splice_region_variant Exon 10 of 12 5 NM_030971.6 ENSP00000377103.1 Q9BWM7

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000399
AC:
10
AN:
250934
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135670
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1461442
Hom.:
0
Cov.:
34
AF XY:
0.0000371
AC XY:
27
AN XY:
727058
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000820
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.784C>T (p.R262C) alteration is located in exon 10 (coding exon 9) of the SFXN3 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the arginine (R) at amino acid position 262 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
Benign
0.14
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
23
DANN
Uncertain
0.99
Eigen
Benign
-0.050
Eigen_PC
Benign
-0.014
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-0.94
T
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-6.4
D;D
REVEL
Benign
0.21
Sift
Benign
0.043
D;D
Sift4G
Uncertain
0.027
D;D
Vest4
0.45
MVP
0.42
MPC
0.32
ClinPred
0.55
D
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.017
dbscSNV1_RF
Benign
0.19
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.

Other links and lift over

dbSNP: rs752580747; hg19: chr10-102798400; COSMIC: COSV56519868; COSMIC: COSV56519868; API