10-102729326-G-T

Position:

• chr10-102729326-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178858.6(SFXN2):​c.439G>T​(p.Ala147Ser) 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: 6.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN2	NM_178858.6	c.439G>T	p.Ala147Ser	missense_variant	5/12	ENST00000369893.10	NP_849189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN2	ENST00000369893.10	c.439G>T	p.Ala147Ser	missense_variant	5/12	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 28, 2024

The c.439G>T (p.A147S) alteration is located in exon 5 (coding exon 4) of the SFXN2 gene. This alteration results from a G to T substitution at nucleotide position 439, causing the alanine (A) at amino acid position 147 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	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	.;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.46	.;N;.
REVEL	Benign	0.17
Sift	Benign	0.12	.;T;.
Sift4G	Benign	0.40	T;T;T
Polyphen		0.29	.;B;.
Vest4		0.43
MutPred		0.64		Gain of disorder (P = 0.0301);Gain of disorder (P = 0.0301);Gain of disorder (P = 0.0301);
MVP		0.14
MPC		0.23
ClinPred		0.85	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: 19

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: chr10-104489083; COSMIC: COSV64011994; COSMIC: COSV64011994;