rs925197

Variant names:

• chr5-175512211-C-T
• rs925197
• NM_022754.7:c.596+15C>T

Variant summary

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

The NM_022754.7(SFXN1):​c.596+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,606,772 control chromosomes in the GnomAD database, including 26,038 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 0.22 (4674 hom., cov: 33)
  • Exomes 𝑓: 0.16 (21364 hom.)
• Consequence: SFXN1 NM_022754.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

Genes affected

SFXN1 (HGNC:16085): (sideroflexin 1) Enables D-serine transmembrane transporter activity and L-serine transmembrane transporter activity. Involved in D-serine transport; L-serine transport; and serine import into mitochondrion. Located in mitochondrion. Is integral component of mitochondrial inner membrane. [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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN1	NM_022754.7	c.596+15C>T		intron_variant	Intron 6 of 10	ENST00000321442.10	NP_073591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN1	ENST00000321442.10	c.596+15C>T		intron_variant	Intron 6 of 10	1	NM_022754.7	ENSP00000316905.5

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33582 AN: 152016 Hom.: 4670 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.194 AC: 48690 AN: 250650 Hom.: 5754 AF XY: 0.196 AC XY: 26606 AN XY: 135490

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.158 AC: 229202 AN: 1454638 Hom.: 21364 Cov.: 28 AF XY: 0.162 AC XY: 117209 AN XY: 724202

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.221 AC: 33619 AN: 152134 Hom.: 4674 Cov.: 33 AF XY: 0.221 AC XY: 16440 AN XY: 74386

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.207

Alfa AF: 0.187 Hom.: 982

Bravo AF: 0.228

Asia WGS AF: 0.314 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.9
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs925197; hg19: chr5-174939214; COSMIC: COSV58493479; COSMIC: COSV58493479;