10-119141113-C-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.*129G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 628,966 control chromosomes in the GnomAD database, including 1,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (554 hom., cov: 32)
  • Exomes 𝑓: 0.021 (596 hom.)
• Consequence: SFXN4 NM_213649.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.30

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=-0.93).
• BP6: Variant 10-119141113-C-T is Benign according to our data. Variant chr10-119141113-C-T is described in ClinVar as [Benign]. Clinvar id is 1237656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.*129G>A		3_prime_UTR_variant	14/14	ENST00000355697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7	c.*129G>A		3_prime_UTR_variant	14/14	1	NM_213649.2	P1
SFXN4	ENST00000484960.5	n.355G>A		non_coding_transcript_exon_variant	3/3	3
SFXN4	ENST00000490417.6	n.606G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8169 AN: 152006 Hom.: 552 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0205 AC: 9784 AN: 476842 Hom.: 596 Cov.: 6 AF XY: 0.0185 AC XY: 4761 AN XY: 257002

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0879

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.0150

Gnomad4 FIN exome AF: 0.000740

Gnomad4 NFE exome AF: 0.000968

Gnomad4 OTH exome AF: 0.0238

GnomAD4 genome AF: 0.0539 AC: 8194 AN: 152124 Hom.: 554 Cov.: 32 AF XY: 0.0539 AC XY: 4008 AN XY: 74360

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0176 Hom.: 157

Bravo AF: 0.0664

Asia WGS AF: 0.0790 AC: 274 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 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.031
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: rs2275110; hg19: chr10-120900625; COSMIC: COSV57460100; COSMIC: COSV57460100;