2-72999005-C-A

Position:

• chr2-72999005-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144579.3(SFXN5):​c.478G>T​(p.Ala160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SFXN5 NM_144579.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

Genes affected

SFXN5 (HGNC:16073): (sideroflexin 5) Predicted to enable citrate transmembrane transporter activity. Predicted to be involved in citrate transport and mitochondrial transmembrane transport. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SFXN5 (HGNC:):

ACMG classification

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=0.09251636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN5	NM_144579.3	c.478G>T	p.Ala160Ser	missense_variant	9/14	ENST00000272433.7	NP_653180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN5	ENST00000272433.7	c.478G>T	p.Ala160Ser	missense_variant	9/14	1	NM_144579.3	ENSP00000272433.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461804 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jun 02, 2023

The c.478G>T (p.A160S) alteration is located in exon 9 (coding exon 9) of the SFXN5 gene. This alteration results from a G to T substitution at nucleotide position 478, causing the alanine (A) at amino acid position 160 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	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.050	N;N;N
REVEL	Benign	0.063
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.15	T;T;.
Polyphen		0.0020	B;B;.
Vest4		0.27
MutPred		0.41		Gain of disorder (P = 0.0239);Gain of disorder (P = 0.0239);.;
MVP		0.19
MPC		0.29
ClinPred		0.73	D
GERP RS		4.1
Varity_R		0.051
gMVP		0.28

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: chr2-73226134;