10-119140986-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_213649.2(SFXN4):c.*256G>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 0.00148 in 392,108 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: SFXN4 NM_213649.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.60

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=-0.9).
• BP6: Variant 10-119140986-C-T is Benign according to our data. Variant chr10-119140986-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1186555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00308 (468/152184) while in subpopulation AFR AF= 0.0107 (445/41504). AF 95% confidence interval is 0.0099. There are 2 homozygotes in gnomad4. There are 234 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.*256G>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.*256G>A		3_prime_UTR_variant	14/14	1	NM_213649.2	P1
SFXN4	ENST00000484960.5	n.482G>A		non_coding_transcript_exon_variant	3/3	3
SFXN4	ENST00000490417.6	n.733G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152066 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000475 AC: 114 AN: 239924 Hom.: 0 Cov.: 0 AF XY: 0.000421 AC XY: 52 AN XY: 123544

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.000526

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000147

Gnomad4 OTH exome AF: 0.000915

GnomAD4 genome AF: 0.00308 AC: 468 AN: 152184 Hom.: 2 Cov.: 32 AF XY: 0.00314 AC XY: 234 AN XY: 74418

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000314 Hom.: 1

Bravo AF: 0.00333

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.017
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs115303392; hg19: chr10-120900498;