rs2421099

Positions:

• chr2-73068935-T-A
• chr2-73068935-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144579.3(SFXN5):​c.102+2669A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 149,182 control chromosomes in the GnomAD database, including 1,861 homozygotes. 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: 𝑓 0.15 (1861 hom., cov: 30)
• Consequence: SFXN5 NM_144579.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN5	NM_144579.3	c.102+2669A>T		intron_variant		ENST00000272433.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN5	ENST00000272433.7	c.102+2669A>T		intron_variant		1	NM_144579.3	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21680 AN: 149062 Hom.: 1865 Cov.: 30

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0661

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.0865

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.145 AC: 21686 AN: 149182 Hom.: 1861 Cov.: 30 AF XY: 0.153 AC XY: 11089 AN XY: 72644

Gnomad4 AFR AF: 0.0889

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.146

Alfa AF: 0.126 Hom.: 176

Bravo AF: 0.140

Asia WGS AF: 0.273 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.3
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs2421099; hg19: chr2-73296064;