rs2275112

chr10-119158104-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213649.2(SFXN4):c.361-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,589,208 control chromosomes in the GnomAD database, including 98,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7566 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90593 hom.)
• Consequence: SFXN4 NM_213649.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0650

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-119158104-G-A is Benign according to our data. Variant chr10-119158104-G-A is described in ClinVar as [Benign]. Clinvar id is 1292078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.361-42C>T		intron_variant		ENST00000355697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7	c.361-42C>T		intron_variant		1	NM_213649.2	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45456 AN: 151926 Hom.: 7569 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.308

GnomAD3 exomes AF: 0.332 AC: 83235 AN: 251032 Hom.: 14641 AF XY: 0.340 AC XY: 46150 AN XY: 135782

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.397

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.351 AC: 504415 AN: 1437162 Hom.: 90593 Cov.: 26 AF XY: 0.353 AC XY: 253143 AN XY: 716510

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.299 AC: 45453 AN: 152046 Hom.: 7566 Cov.: 32 AF XY: 0.304 AC XY: 22587 AN XY: 74306

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.309

Alfa AF: 0.331 Hom.: 1896

Bravo AF: 0.274

Asia WGS AF: 0.304 AC: 1055 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.5
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2275112; hg19: chr10-120917616; COSMIC: COSV57459383; COSMIC: COSV57459383;