chr10-101038646-C-A

Variant names:

• chr10-101038646-C-A
• rs201018843
• NM_030971.6:c.775C>A

Variant summary

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

The NM_030971.6(SFXN3):​c.775C>A​(p.Arg259Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R259C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SFXN3 NM_030971.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

Genes affected

SFXN3 (HGNC:16087): (sideroflexin 3) Enables serine transmembrane transporter activity. Involved in serine import into mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
SFXN3	NM_030971.6	c.775C>A	p.Arg259Ser	missense_variant	Exon 10 of 12	ENST00000393459.6	NP_112233.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN3	ENST00000393459.6	c.775C>A	p.Arg259Ser	missense_variant	Exon 10 of 12	5	NM_030971.6	ENSP00000377103.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250900 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135654

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461404 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727042

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.76	N;N
REVEL	Benign	0.073
Sift	Benign	0.35	T;T
Sift4G	Benign	0.40	T;T
Vest4		0.46
MutPred		0.41		.;Loss of glycosylation at P264 (P = 0.08);
MVP		0.41
MPC		0.24
ClinPred		0.22	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201018843; hg19: chr10-102798403;