10-119141507-CTTTTTTT-CTTTTTTTTT

Variant names:

• chr10-119141507-C-CTT
• rs1234472904
• NM_213649.2:c.937-190_937-189dupAA

Variant summary

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

The NM_213649.2(SFXN4):​c.937-190_937-189dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.021 (139 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-CTT is Benign according to our data. Variant chr10-119141507-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1256640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0694 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.937-190_937-189dupAA		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.1076-190_1076-189dupAA		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_937-188insAA		intron	N/A	ENSP00000347924.2	Q6P4A7-1
	SFXN4	ENST00000955059.1		c.937-195_937-194insAA		intron	N/A	ENSP00000625118.1
	SFXN4	ENST00000461438.5	TSL:5	n.966-189_966-188insAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 2393 AN: 113306 Hom.: 139 Cov.: 19

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.00519

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00367

Gnomad EAS AF: 0.00180

Gnomad SAS AF: 0.00792

Gnomad FIN AF: 0.000568

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00361

Gnomad OTH AF: 0.0184

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

GnomAD4 genome AF: 0.0211 AC: 2396 AN: 113312 Hom.: 139 Cov.: 19 AF XY: 0.0212 AC XY: 1134 AN XY: 53520

African (AFR) AF: 0.0720 AC: 2010 AN: 27920

American (AMR) AF: 0.00975 AC: 101 AN: 10364

Ashkenazi Jewish (ASJ) AF: 0.00367 AC: 11 AN: 3000

East Asian (EAS) AF: 0.00180 AC: 7 AN: 3886

South Asian (SAS) AF: 0.00795 AC: 27 AN: 3396

European-Finnish (FIN) AF: 0.000568 AC: 3 AN: 5284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.00361 AC: 206 AN: 57048

Other (OTH) AF: 0.0183 AC: 27 AN: 1478

Alfa AF: 0.00102 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

Splicing

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

Other links and lift over

dbSNP: rs1234472904; hg19: chr10-120901019;