rs2297696

Positions:

• chr10-119156955-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213649.2(SFXN4):​c.538-199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,840 control chromosomes in the GnomAD database, including 7,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.30 (7562 hom., cov: 31)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.347

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-119156955-A-G is Benign according to our data. Variant chr10-119156955-A-G is described in ClinVar as [Benign]. Clinvar id is 667486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFXN4	NM_213649.2	c.538-199T>C		intron_variant		ENST00000355697.7	NP_998814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFXN4	ENST00000355697.7	c.538-199T>C		intron_variant		1	NM_213649.2	ENSP00000347924.2
SFXN4	ENST00000369131.8	c.190-199T>C		intron_variant		5		ENSP00000358127.4
SFXN4	ENST00000461438.5	n.567-199T>C		intron_variant		5
SFXN4	ENST00000466218.5	n.487-199T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45406 AN: 151722 Hom.: 7566 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.299 AC: 45401 AN: 151840 Hom.: 7562 Cov.: 31 AF XY: 0.304 AC XY: 22547 AN XY: 74154

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.309

Alfa AF: 0.345 Hom.: 18714

Bravo AF: 0.274

Asia WGS AF: 0.304 AC: 1055 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2297696; hg19: chr10-120916467;