rs6897931

Positions:

• chr5-175522472-C-A
• chr5-175522472-C-T

Variant summary

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

The NM_022754.7(SFXN1):​c.872+50C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,563,470 control chromosomes in the GnomAD database, including 1,148 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 0.046 (269 hom., cov: 32)
  • Exomes 𝑓: 0.018 (879 hom.)
• Consequence: SFXN1 NM_022754.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952

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]

SFXN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN1	NM_022754.7	c.872+50C>A		intron_variant		ENST00000321442.10	NP_073591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN1	ENST00000321442.10	c.872+50C>A		intron_variant		1	NM_022754.7	ENSP00000316905.5
SFXN1	ENST00000507823.5	n.*722C>A		non_coding_transcript_exon_variant	10/10	2		ENSP00000421982.1
SFXN1	ENST00000507823.5	n.*722C>A		3_prime_UTR_variant	10/10	2		ENSP00000421982.1
SFXN1	ENST00000421887.2	n.131+50C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6964 AN: 151784 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00915

Gnomad OTH AF: 0.0465

GnomAD3 exomes AF: 0.0406 AC: 9301 AN: 229368 Hom.: 437 AF XY: 0.0379 AC XY: 4724 AN XY: 124524

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.0197

Gnomad EAS exome AF: 0.0216

Gnomad SAS exome AF: 0.0765

Gnomad FIN exome AF: 0.0186

Gnomad NFE exome AF: 0.00973

Gnomad OTH exome AF: 0.0263

GnomAD4 exome AF: 0.0182 AC: 25636 AN: 1411568 Hom.: 879 Cov.: 23 AF XY: 0.0192 AC XY: 13546 AN XY: 704204

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.0188

Gnomad4 EAS exome AF: 0.0173

Gnomad4 SAS exome AF: 0.0746

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.00737

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0459 AC: 6978 AN: 151902 Hom.: 269 Cov.: 32 AF XY: 0.0478 AC XY: 3547 AN XY: 74240

Gnomad4 AFR AF: 0.0979

Gnomad4 AMR AF: 0.0974

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.00915

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0183 Hom.: 64

Bravo AF: 0.0545

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.59
DANN	Benign	0.46

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: rs6897931; hg19: chr5-174949475;