10-119141464-ATTTTT-ATTTT

Variant names:

• chr10-119141464-AT-A
• rs34287145
• NM_213649.2:c.937-146delA

Variant summary

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

The NM_213649.2(SFXN4):​c.937-146delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 322,480 control chromosomes in the GnomAD database, including 5,692 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4001 hom., cov: 0)
  • Exomes 𝑓: 0.17 (1691 hom.)
• 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-AT-A is Benign according to our data. Variant chr10-119141464-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1268158.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 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.937-146delA		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.1076-146delA		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.224 AC: 32540 AN: 144974 Hom.: 4005 Cov.: 0

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.302

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.170 AC: 30142 AN: 177412 Hom.: 1691 AF XY: 0.171 AC XY: 16253 AN XY: 95160

African (AFR) AF: 0.287 AC: 1042 AN: 3626

American (AMR) AF: 0.204 AC: 988 AN: 4848

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 1114 AN: 5134

East Asian (EAS) AF: 0.231 AC: 2725 AN: 11772

South Asian (SAS) AF: 0.235 AC: 3387 AN: 14424

European-Finnish (FIN) AF: 0.136 AC: 2030 AN: 14956

Middle Eastern (MID) AF: 0.279 AC: 211 AN: 756

European-Non Finnish (NFE) AF: 0.151 AC: 16875 AN: 111772

Other (OTH) AF: 0.175 AC: 1770 AN: 10124

GnomAD4 genome AF: 0.224 AC: 32553 AN: 145068 Hom.: 4001 Cov.: 0 AF XY: 0.226 AC XY: 15828 AN XY: 70134

African (AFR) AF: 0.331 AC: 12789 AN: 38658

American (AMR) AF: 0.237 AC: 3398 AN: 14358

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 814 AN: 3452

East Asian (EAS) AF: 0.238 AC: 1179 AN: 4954

South Asian (SAS) AF: 0.277 AC: 1296 AN: 4682

European-Finnish (FIN) AF: 0.129 AC: 1149 AN: 8876

Middle Eastern (MID) AF: 0.295 AC: 85 AN: 288

European-Non Finnish (NFE) AF: 0.168 AC: 11241 AN: 66888

Other (OTH) AF: 0.241 AC: 486 AN: 2018

Alfa AF: 0.124 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;