10-102727082-T-C

Position:

• chr10-102727082-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_178858.6(SFXN2):​c.257T>C​(p.Met86Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFXN2 NM_178858.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN2	NM_178858.6	c.257T>C	p.Met86Thr	missense_variant	3/12	ENST00000369893.10	NP_849189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN2	ENST00000369893.10	c.257T>C	p.Met86Thr	missense_variant	3/12	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

Apr 24, 2024

The c.257T>C (p.M86T) 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 257, causing the methionine (M) at amino acid position 86 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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;T;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.88	D;D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Pathogenic	3.1	.;M;.;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.0	.;D;.;.;.
REVEL	Uncertain	0.63
Sift	Benign	0.031	.;D;.;.;.
Sift4G	Uncertain	0.014	D;D;.;D;D
Polyphen		0.95	.;P;.;.;.
Vest4		0.96
MutPred		0.78		Gain of methylation at K85 (P = 0.025);Gain of methylation at K85 (P = 0.025);.;Gain of methylation at K85 (P = 0.025);Gain of methylation at K85 (P = 0.025);
MVP		0.61
MPC		0.71
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.84

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: chr10-104486839;