rs11198804

Variant names:

• chr10-119150273-C-T
• rs11198804
• NM_213649.2:c.733-2413G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213649.2(SFXN4):​c.733-2413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,890 control chromosomes in the GnomAD database, including 6,124 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6124 hom., cov: 31)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.733-2413G>A		intron_variant	Intron 11 of 13	ENST00000355697.7	NP_998814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFXN4	ENST00000355697.7	c.733-2413G>A		intron_variant	Intron 11 of 13	1	NM_213649.2	ENSP00000347924.2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42439 AN: 151770 Hom.: 6120 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.280 AC: 42480 AN: 151890 Hom.: 6124 Cov.: 31 AF XY: 0.279 AC XY: 20687 AN XY: 74222

African (AFR) AF: 0.298 AC: 12326 AN: 41404

American (AMR) AF: 0.219 AC: 3345 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2483 AN: 5168

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4812

European-Finnish (FIN) AF: 0.249 AC: 2630 AN: 10546

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18404 AN: 67930

Other (OTH) AF: 0.289 AC: 610 AN: 2108

Alfa AF: 0.258 Hom.: 838

Bravo AF: 0.281

Asia WGS AF: 0.308 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.063
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: rs11198804; hg19: chr10-120909785;