chr10-102726662-A-C

Position:

• chr10-102726662-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178858.6(SFXN2):​c.26A>C​(p.Asn9Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFXN2 NM_178858.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14

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 (HGNC:):

ACMG classification

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=0.35542208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN2	NM_178858.6	c.26A>C	p.Asn9Thr	missense_variant	2/12	ENST00000369893.10	NP_849189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN2	ENST00000369893.10	c.26A>C	p.Asn9Thr	missense_variant	2/12	1	NM_178858.6	ENSP00000358909.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.26A>C (p.N9T) alteration is located in exon 2 (coding exon 1) of the SFXN2 gene. This alteration results from a A to C substitution at nucleotide position 26, causing the asparagine (N) at amino acid position 9 to be replaced by a threonine (T). 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	0.22
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	.;T;T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	.;M;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.9	.;D;.;.;.
REVEL	Benign	0.17
Sift	Uncertain	0.0020	.;D;.;.;.
Sift4G	Uncertain	0.0080	D;D;.;T;D
Polyphen		0.33	.;B;.;.;.
Vest4		0.31
MutPred		0.39		Gain of phosphorylation at N9 (P = 0.0423);Gain of phosphorylation at N9 (P = 0.0423);.;Gain of phosphorylation at N9 (P = 0.0423);Gain of phosphorylation at N9 (P = 0.0423);
MVP		0.39
MPC		0.20
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.36
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104486419;