rs3740558

chr10-119159667-G-Achr10-119159667-G-Cchr10-119159667-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_213649.2(SFXN4):c.360+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,558,406 control chromosomes in the GnomAD database, including 197,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18002 hom., cov: 31)
  • Exomes 𝑓: 0.50 (179039 hom.)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-119159667-G-A is Benign according to our data. Variant chr10-119159667-G-A is described in ClinVar as [Benign]. Clinvar id is 1245985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.360+61C>T		intron_variant		ENST00000355697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7	c.360+61C>T		intron_variant		1	NM_213649.2	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73341 AN: 151806 Hom.: 17985 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.502 AC: 706418 AN: 1406482 Hom.: 179039 AF XY: 0.500 AC XY: 351604 AN XY: 702924

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.483 AC: 73395 AN: 151924 Hom.: 18002 Cov.: 31 AF XY: 0.481 AC XY: 35699 AN XY: 74244

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.486

Alfa AF: 0.473 Hom.: 3066

Bravo AF: 0.487

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.5
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3740558; hg19: chr10-120919179;