chr10-119141507-CTT-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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

• Frequency: Genomes: 𝑓 0.0035 (2 hom., cov: 19)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Likely 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-CTT-C is Benign according to our data. Variant chr10-119141507-CTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1211805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0035 (397/113304) while in subpopulation AFR AF = 0.0128 (358/27890). AF 95% confidence interval is 0.0117. There are 2 homozygotes in GnomAd4. There are 178 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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_937-189delAA		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.1076-190_1076-189delAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN4	ENST00000355697.7	TSL:1 MANE Select	c.937-190_937-189delAA		intron	N/A	ENSP00000347924.2	Q6P4A7-1
	SFXN4	ENST00000955059.1		c.937-196_937-195delAA		intron	N/A	ENSP00000625118.1
	SFXN4	ENST00000461438.5	TSL:5	n.966-190_966-189delAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 394 AN: 113298 Hom.: 2 Cov.: 19

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00174

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00133

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.00205

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

GnomAD4 genome AF: 0.00350 AC: 397 AN: 113304 Hom.: 2 Cov.: 19 AF XY: 0.00333 AC XY: 178 AN XY: 53512

African (AFR) AF: 0.0128 AC: 358 AN: 27890

American (AMR) AF: 0.00174 AC: 18 AN: 10364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3000

East Asian (EAS) AF: 0.00 AC: 0 AN: 3888

South Asian (SAS) AF: 0.00 AC: 0 AN: 3398

European-Finnish (FIN) AF: 0.00133 AC: 7 AN: 5278

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

European-Non Finnish (NFE) AF: 0.000193 AC: 11 AN: 57072

Other (OTH) AF: 0.00203 AC: 3 AN: 1476

Alfa AF: 0.00 Hom.: 113

ClinVar

ClinVar submissions

Significance: Likely 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

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;