Genetic Variant SFXN4:c.937-189delA (chr10-119141507-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_213649.2(SFXN4):c.937-189delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 48 hom., cov: 19)

Consequence

SFXN4
NM_213649.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.953

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

SFXN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 10-119141507-CT-C is Benign according to our data. Variant chr10-119141507-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1256922.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213649.2. 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
	SFXN4	NM_213649.2	MANE Select	c.937-189delA		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.1076-189delA		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFXN4	ENST00000355697.7	TSL:1 MANE Select	c.937-189delA	intron	N/A	ENSP00000347924.2	Q6P4A7-1
SFXN4	ENST00000955059.1		c.937-195delA	intron	N/A	ENSP00000625118.1
SFXN4	ENST00000461438.5	TSL:5	n.966-189delA	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

2475

AN:

113322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0803

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.000666

Gnomad EAS

AF:

0.00103

Gnomad SAS

AF:

0.00117

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.0163

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.0150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0218

AC:

2471

AN:

113326

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1160

AN XY:

53524

show subpopulations

African (AFR)

AF:

0.0801

AC:

2234

AN:

27888

American (AMR)

AF:

0.0110

AC:

114

AN:

10370

Ashkenazi Jewish (ASJ)

AF:

0.000666

AC:

AN:

3002

East Asian (EAS)

AF:

0.00103

AC:

AN:

3888

South Asian (SAS)

AF:

0.000883

AC:

AN:

3398

European-Finnish (FIN)

AF:

0.00303

AC:

AN:

5288

Middle Eastern (MID)

AF:

0.0181

AC:

AN:

166

European-Non Finnish (NFE)

AF:

0.00128

AC:

AN:

57076

Other (OTH)

AF:

0.0149

AC:

AN:

1478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

183

275

366

458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00

Hom.:

113

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over