10-119141464-ATTTTT-ATTT

Variant names:

• chr10-119141464-ATT-A
• rs34287145
• NM_213649.2:c.937-147_937-146delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_213649.2(SFXN4):​c.937-147_937-146delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 178,794 control chromosomes in the GnomAD database, including 57,500 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (39588 hom., cov: 0)
  • Exomes 𝑓: 0.81 (57500 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850
• Publications: 0 publications found

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

ACMG classification

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

• BP6: Variant 10-119141464-ATT-A is Benign according to our data. Variant chr10-119141464-ATT-A is described in ClinVar as Benign. ClinVar VariationId is 1225080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.827 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.937-147_937-146delAA		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.1076-147_1076-146delAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN4	ENST00000355697.7	TSL:1 MANE Select	c.937-147_937-146delAA		intron	N/A	ENSP00000347924.2	Q6P4A7-1
	SFXN4	ENST00000955059.1		c.937-153_937-152delAA		intron	N/A	ENSP00000625118.1
	SFXN4	ENST00000461438.5	TSL:5	n.966-147_966-146delAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.724 AC: 105103 AN: 145120 Hom.: 39568 Cov.: 0

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.808 AC: 144546 AN: 178794 Hom.: 57500 AF XY: 0.808 AC XY: 77508 AN XY: 95922

African (AFR) AF: 0.509 AC: 1855 AN: 3642

American (AMR) AF: 0.767 AC: 3751 AN: 4890

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 3947 AN: 5172

East Asian (EAS) AF: 0.755 AC: 8937 AN: 11838

South Asian (SAS) AF: 0.746 AC: 10836 AN: 14518

European-Finnish (FIN) AF: 0.851 AC: 12823 AN: 15066

Middle Eastern (MID) AF: 0.690 AC: 522 AN: 756

European-Non Finnish (NFE) AF: 0.832 AC: 93742 AN: 112688

Other (OTH) AF: 0.795 AC: 8133 AN: 10224

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.724 AC: 105158 AN: 145212 Hom.: 39588 Cov.: 0 AF XY: 0.724 AC XY: 50862 AN XY: 70228

African (AFR) AF: 0.491 AC: 18996 AN: 38694

American (AMR) AF: 0.743 AC: 10680 AN: 14376

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2624 AN: 3448

East Asian (EAS) AF: 0.761 AC: 3774 AN: 4960

South Asian (SAS) AF: 0.721 AC: 3385 AN: 4692

European-Finnish (FIN) AF: 0.868 AC: 7733 AN: 8904

Middle Eastern (MID) AF: 0.681 AC: 196 AN: 288

European-Non Finnish (NFE) AF: 0.830 AC: 55535 AN: 66932

Other (OTH) AF: 0.721 AC: 1459 AN: 2024

Alfa AF: 0.856 Hom.: 35

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.085
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: rs34287145; hg19: chr10-120900976;