rs2275111

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_213649.2(SFXN4):c.415-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,613,640 control chromosomes in the GnomAD database, including 203,917 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18105 hom., cov: 34)

Exomes 𝑓: 0.50 ( 185812 hom. )

Consequence

SFXN4
NM_213649.2 splice_region, intron

Scores

Splicing: ADA: 0.00002648

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.19

Publications

31 publications found

Variant links:

Genes affected

SFXN4 (HGNC:16088): (sideroflexin 4) This gene encodes a member of the sideroflexin family. The encoded protein is a transmembrane protein of the inner mitochondrial membrane, and is required for mitochondrial respiratory homeostasis and erythropoiesis. Mutations in this gene are associated with mitochondriopathy and macrocytic anemia. Alternatively spliced transcript variants have been found in this gene. [provided by RefSeq, Jan 2014]

SFXN4 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

SFXN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-119157933-G-A is Benign according to our data. Variant chr10-119157933-G-A is described in ClinVar as Benign. ClinVar VariationId is 380007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2 link	c.415-6C>T		splice_region_variant, intron_variant	Intron 7 of 13	ENST00000355697.7	NP_998814.1	Q6P4A7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN4	ENST00000355697.7 link	c.415-6C>T		splice_region_variant, intron_variant	Intron 7 of 13	1	NM_213649.2	ENSP00000347924.2		Q6P4A7-1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73617

AN:

152032

Hom.:

18089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.488

GnomAD2 exomes

AF:

0.499

AC:

125461

AN:

251420

AF XY:

0.497

show subpopulations

Gnomad AFR exome

AF:

0.442

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.728

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.501

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.502

AC:

733778

AN:

1461490

Hom.:

185812

Cov.:

AF XY:

0.500

AC XY:

363626

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.432

AC:

14477

AN:

33474

American (AMR)

AF:

0.466

AC:

20831

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

14500

AN:

26132

East Asian (EAS)

AF:

0.692

AC:

27463

AN:

39700

South Asian (SAS)

AF:

0.444

AC:

38329

AN:

86242

European-Finnish (FIN)

AF:

0.439

AC:

23448

AN:

53414

Middle Eastern (MID)

AF:

0.462

AC:

2667

AN:

5768

European-Non Finnish (NFE)

AF:

0.505

AC:

561129

AN:

1111654

Other (OTH)

AF:

0.512

AC:

30934

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

20124

40248

60373

80497

100621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16434

32868

49302

65736

82170

<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:

0.484

AC:

73672

AN:

152150

Hom.:

18105

Cov.:

AF XY:

0.482

AC XY:

35863

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.442

AC:

18337

AN:

41482

American (AMR)

AF:

0.482

AC:

7368

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1947

AN:

3468

East Asian (EAS)

AF:

0.717

AC:

3719

AN:

5184

South Asian (SAS)

AF:

0.452

AC:

2182

AN:

4828

European-Finnish (FIN)

AF:

0.445

AC:

4711

AN:

10580

Middle Eastern (MID)

AF:

0.517

AC:

151

AN:

292

European-Non Finnish (NFE)

AF:

0.497

AC:

33836

AN:

68014

Other (OTH)

AF:

0.489

AC:

1032

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2005

4010

6016

8021

10026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.498

Hom.:

86488

Bravo

AF:

0.489

Asia WGS

AF:

0.548

AC:

1903

AN:

3478

EpiCase

AF:

0.502

EpiControl

AF:

0.502

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.15

(source)

DANN

Benign

0.36

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0020

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over