10-119141464-AT-A

Variant summary

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

The NM_213649.2(SFXN4):c.937-146del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 322,480 control chromosomes in the GnomAD database, including 5,692 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4001 hom., cov: 0)
  • Exomes 𝑓: 0.17 (1691 hom.)
• 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-AT-A is Benign according to our data. Variant chr10-119141464-AT-A is described in ClinVar as [Benign]. Clinvar id is 1268158.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.224 AC: 32540 AN: 144974 Hom.: 4005 Cov.: 0

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.302

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.170 AC: 30142 AN: 177412 Hom.: 1691 AF XY: 0.171 AC XY: 16253 AN XY: 95160

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.224 AC: 32553 AN: 145068 Hom.: 4001 Cov.: 0 AF XY: 0.226 AC XY: 15828 AN XY: 70134

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.241

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;