10-119141464-ATT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_213649.2(SFXN4):c.937-147_937-146del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 178,794 control chromosomes in the GnomAD database, including 57,500 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (39588 hom., cov: 0)
  • Exomes 𝑓: 0.81 (57500 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850

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 -10 ACMG points.

• BP6: Variant 10-119141464-ATT-A is Benign according to our data. Variant chr10-119141464-ATT-A is described in ClinVar as [Benign]. Clinvar id is 1225080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.937-147_937-146del		intron_variant		ENST00000355697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7	c.937-147_937-146del		intron_variant		1	NM_213649.2	P1
SFXN4	ENST00000461438.5	n.966-147_966-146del		intron_variant, non_coding_transcript_variant		5
SFXN4	ENST00000484960.5	n.149-147_149-146del		intron_variant, non_coding_transcript_variant		3
SFXN4	ENST00000490417.6	n.400-147_400-146del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 105103 AN: 145120 Hom.: 39568 Cov.: 0

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.808 AC: 144546 AN: 178794 Hom.: 57500 AF XY: 0.808 AC XY: 77508 AN XY: 95922

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.755

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.795

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.724 AC: 105158 AN: 145212 Hom.: 39588 Cov.: 0 AF XY: 0.724 AC XY: 50862 AN XY: 70228

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.721

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

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs34287145; hg19: chr10-120900976;