rs2275112

Variant names:

• chr10-119158104-G-A
• rs2275112
• NM_213649.2:c.361-42C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213649.2(SFXN4):​c.361-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,589,208 control chromosomes in the GnomAD database, including 98,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7566 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90593 hom.)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0650
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-119158104-G-A is Benign according to our data. Variant chr10-119158104-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 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.361-42C>T		intron	N/A	NP_998814.1	Q6P4A7-1
	SFXN4	NR_110305.1		n.379-42C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFXN4	ENST00000355697.7	TSL:1 MANE Select	c.361-42C>T		intron	N/A	ENSP00000347924.2	Q6P4A7-1
	SFXN4	ENST00000955059.1		c.361-42C>T		intron	N/A	ENSP00000625118.1
	SFXN4	ENST00000369131.8	TSL:5	c.13-42C>T		intron	N/A	ENSP00000358127.4	B1AMV7

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45456 AN: 151926 Hom.: 7569 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.308

GnomAD2 exomes AF: 0.332 AC: 83235 AN: 251032 AF XY: 0.340

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.351 AC: 504415 AN: 1437162 Hom.: 90593 Cov.: 26 AF XY: 0.353 AC XY: 253143 AN XY: 716510

African (AFR) AF: 0.161 AC: 5313 AN: 33006

American (AMR) AF: 0.286 AC: 12761 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 7952 AN: 25994

East Asian (EAS) AF: 0.207 AC: 8198 AN: 39602

South Asian (SAS) AF: 0.401 AC: 34346 AN: 85710

European-Finnish (FIN) AF: 0.456 AC: 24324 AN: 53386

Middle Eastern (MID) AF: 0.325 AC: 1859 AN: 5720

European-Non Finnish (NFE) AF: 0.358 AC: 390282 AN: 1089504

Other (OTH) AF: 0.325 AC: 19380 AN: 59560

GnomAD4 genome AF: 0.299 AC: 45453 AN: 152046 Hom.: 7566 Cov.: 32 AF XY: 0.304 AC XY: 22587 AN XY: 74306

African (AFR) AF: 0.164 AC: 6787 AN: 41492

American (AMR) AF: 0.286 AC: 4363 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1052 AN: 3470

East Asian (EAS) AF: 0.168 AC: 872 AN: 5178

South Asian (SAS) AF: 0.390 AC: 1880 AN: 4818

European-Finnish (FIN) AF: 0.457 AC: 4813 AN: 10540

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24594 AN: 67970

Other (OTH) AF: 0.309 AC: 653 AN: 2114

Alfa AF: 0.310 Hom.: 2927

Bravo AF: 0.274

Asia WGS AF: 0.304 AC: 1055 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.51
PhyloP100		0.065
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2275112; hg19: chr10-120917616; COSMIC: COSV57459383; COSMIC: COSV57459383;