Genetic Variant SFXN1:c.872+50C>A (chr5-175522472-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.952

Publications

2 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFXN1	NM_022754.7	MANE Select	c.872+50C>A	intron	N/A	NP_073591.2
SFXN1	NM_001322977.2		c.872+50C>A	intron	N/A	NP_001309906.1	Q9H9B4
SFXN1	NM_001322978.2		c.689+50C>A	intron	N/A	NP_001309907.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFXN1	ENST00000321442.10	TSL:1 MANE Select	c.872+50C>A	intron	N/A	ENSP00000316905.5	Q9H9B4
SFXN1	ENST00000873630.1		c.872+50C>A	intron	N/A	ENSP00000543689.1
SFXN1	ENST00000939193.1		c.872+50C>A	intron	N/A	ENSP00000609252.1

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6964

AN:

151784

Hom.:

268

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0406

AC:

9301

AN:

229368

AF XY:

0.0379

show subpopulations

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 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.:

AF XY:

0.0192

AC XY:

13546

AN XY:

704204

show subpopulations

African (AFR)

AF:

0.103

AC:

3265

AN:

31698

American (AMR)

AF:

0.121

AC:

4627

AN:

38260

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

472

AN:

25044

East Asian (EAS)

AF:

0.0173

AC:

677

AN:

39244

South Asian (SAS)

AF:

0.0746

AC:

6072

AN:

81346

European-Finnish (FIN)

AF:

0.0167

AC:

856

AN:

51128

Middle Eastern (MID)

AF:

0.0406

AC:

228

AN:

5614

European-Non Finnish (NFE)

AF:

0.00737

AC:

7964

AN:

1080654

Other (OTH)

AF:

0.0252

AC:

1475

AN:

58580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1155

2311

3466

4622

5777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0459

AC:

6978

AN:

151902

Hom.:

269

Cov.:

AF XY:

0.0478

AC XY:

3547

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.0979

AC:

4055

AN:

41416

American (AMR)

AF:

0.0974

AC:

1486

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3464

East Asian (EAS)

AF:

0.0230

AC:

119

AN:

5178

South Asian (SAS)

AF:

0.0742

AC:

357

AN:

4810

European-Finnish (FIN)

AF:

0.0175

AC:

184

AN:

10486

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00915

AC:

622

AN:

67982

Other (OTH)

AF:

0.0460

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

314

628

943

1257

1571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0237

Hom.:

159

Bravo

AF:

0.0545

Asia WGS

AF:

0.0680

AC:

234

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.59

(source)

DANN

Benign

0.46

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over