Variant 10-102727139-T-C 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_178858.6(SFXN2):c.314T>C(p.Phe105Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,449,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SFXN2
NM_178858.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

SFXN2 (HGNC:16086): (sideroflexin 2) Predicted to enable serine transmembrane transporter activity. Involved in mitochondrial transmembrane transport. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SFXN2 links:

SFXN2 (HGNC:):

SFXN2 links:

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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=0.18184057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN2	NM_178858.6 linkuse as main transcript	c.314T>C	p.Phe105Ser	missense_variant	3/12	ENST00000369893.10	NP_849189.1	Q96NB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN2	ENST00000369893.10 linkuse as main transcript	c.314T>C	p.Phe105Ser	missense_variant	3/12	1	NM_178858.6	ENSP00000358909.4		Q96NB2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251160

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

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:

0.00000345

AC:

AN:

1449896

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

May 03, 2023

The c.314T>C (p.F105S) alteration is located in exon 3 (coding exon 2) of the SFXN2 gene. This alteration results from a T to C substitution at nucleotide position 314, causing the phenylalanine (F) at amino acid position 105 to be replaced by a serine (S). 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

0.33

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

.;T;T;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

D;D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.18

.;N;.;.;.

REVEL

Benign

0.15

Sift

Benign

0.12

.;T;.;.;.

Sift4G

Benign

0.44

T;T;.;T;T

Polyphen

0.018

.;B;.;.;.

Vest4

0.78

MutPred

0.63

Gain of catalytic residue at F105 (P = 0.0038);Gain of catalytic residue at F105 (P = 0.0038);.;Gain of catalytic residue at F105 (P = 0.0038);Gain of catalytic residue at F105 (P = 0.0038);

MVP

0.16

MPC

0.51

ClinPred

0.13

GERP RS

1.7

Varity_R

0.32

gMVP

0.73

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