rs925197

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022754.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN1	NM_022754.7	MANE Select	c.596+15C>T		intron	N/A	NP_073591.2
	SFXN1	NM_001322977.2		c.596+15C>T		intron	N/A	NP_001309906.1
	SFXN1	NM_001322978.2		c.413+15C>T		intron	N/A	NP_001309907.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN1	ENST00000321442.10	TSL:1 MANE Select	c.596+15C>T		intron	N/A	ENSP00000316905.5
	SFXN1	ENST00000873630.1		c.596+15C>T		intron	N/A	ENSP00000543689.1
	SFXN1	ENST00000939193.1		c.596+15C>T		intron	N/A	ENSP00000609252.1

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

GnomAD2 exomes AF: 0.194 AC: 48690 AN: 250650 AF XY: 0.196

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 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

African (AFR) AF: 0.390 AC: 13007 AN: 33336

American (AMR) AF: 0.176 AC: 7871 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5146 AN: 26076

East Asian (EAS) AF: 0.233 AC: 9238 AN: 39654

South Asian (SAS) AF: 0.332 AC: 28531 AN: 85966

European-Finnish (FIN) AF: 0.139 AC: 7406 AN: 53276

Middle Eastern (MID) AF: 0.226 AC: 1301 AN: 5754

European-Non Finnish (NFE) AF: 0.132 AC: 146292 AN: 1105780

Other (OTH) AF: 0.173 AC: 10410 AN: 60166

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

African (AFR) AF: 0.389 AC: 16129 AN: 41456

American (AMR) AF: 0.165 AC: 2528 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1152 AN: 5180

South Asian (SAS) AF: 0.351 AC: 1691 AN: 4824

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10582

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.137 AC: 9343 AN: 68014

Other (OTH) AF: 0.207 AC: 438 AN: 2112

Alfa AF: 0.188 Hom.: 1055

Bravo AF: 0.228

Asia WGS AF: 0.314 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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