NM_213649.2:c.937-189dupA

Variant names:

• chr10-119141507-C-CT
• rs1234472904
• NM_213649.2:c.937-189dupA

Variant summary

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

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

• Frequency: Genomes: 𝑓 0.17 (2267 hom., cov: 19)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.953
• 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 10-119141507-C-CT is Benign according to our data. Variant chr10-119141507-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1224878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 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.937-189dupA		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.1076-189dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN4	ENST00000355697.7	TSL:1 MANE Select	c.937-189_937-188insA		intron	N/A	ENSP00000347924.2	Q6P4A7-1
	SFXN4	ENST00000955059.1		c.937-195_937-194insA		intron	N/A	ENSP00000625118.1
	SFXN4	ENST00000461438.5	TSL:5	n.966-189_966-188insA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.174 AC: 19689 AN: 113336 Hom.: 2271 Cov.: 19

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.174 AC: 19680 AN: 113342 Hom.: 2267 Cov.: 19 AF XY: 0.167 AC XY: 8966 AN XY: 53550

African (AFR) AF: 0.179 AC: 5007 AN: 27922

American (AMR) AF: 0.126 AC: 1307 AN: 10366

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 779 AN: 3002

East Asian (EAS) AF: 0.204 AC: 793 AN: 3884

South Asian (SAS) AF: 0.239 AC: 812 AN: 3396

European-Finnish (FIN) AF: 0.0524 AC: 277 AN: 5286

Middle Eastern (MID) AF: 0.193 AC: 32 AN: 166

European-Non Finnish (NFE) AF: 0.180 AC: 10298 AN: 57068

Other (OTH) AF: 0.186 AC: 275 AN: 1478

Alfa AF: 0.0459 Hom.: 113

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		0.95
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: rs1234472904; hg19: chr10-120901019;