chr10-119141464-A-ATT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213649.2(SFXN4):​c.937-147_937-146dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 179,222 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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_937-146dupAA		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.1076-147_1076-146dupAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN4	ENST00000355697.7	TSL:1 MANE Select	c.937-146_937-145insAA		intron	N/A	ENSP00000347924.2	Q6P4A7-1
	SFXN4	ENST00000955059.1		c.937-152_937-151insAA		intron	N/A	ENSP00000625118.1
	SFXN4	ENST00000461438.5	TSL:5	n.966-146_966-145insAA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000112 AC: 2 AN: 179222 Hom.: 0 AF XY: 0.0000104 AC XY: 1 AN XY: 96166

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000546 AC: 2 AN: 3666

American (AMR) AF: 0.00 AC: 0 AN: 4904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5188

East Asian (EAS) AF: 0.00 AC: 0 AN: 11882

South Asian (SAS) AF: 0.00 AC: 0 AN: 14570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 112910

Other (OTH) AF: 0.00 AC: 0 AN: 10248

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.085

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34287145; hg19: chr10-120900976;