rs2275111

chr10-119157933-G-Achr10-119157933-G-Cchr10-119157933-G-T

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.415-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,613,640 control chromosomes in the GnomAD database, including 203,917 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18105 hom., cov: 34)
  • Exomes 𝑓: 0.50 (185812 hom.)
• Consequence: SFXN4 NM_213649.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002648
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.19

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=-0.87).
• BP6: Variant 10-119157933-G-A is Benign according to our data. Variant chr10-119157933-G-A is described in ClinVar as [Benign]. Clinvar id is 380007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFXN4	NM_213649.2	c.415-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000355697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFXN4	ENST00000355697.7	c.415-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_213649.2	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73617 AN: 152032 Hom.: 18089 Cov.: 34

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.488

GnomAD3 exomes AF: 0.499 AC: 125461 AN: 251420 Hom.: 32045 AF XY: 0.497 AC XY: 67553 AN XY: 135878

Gnomad AFR exome AF: 0.442

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.728

Gnomad SAS exome AF: 0.446

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.502 AC: 733778 AN: 1461490 Hom.: 185812 Cov.: 50 AF XY: 0.500 AC XY: 363626 AN XY: 727064

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.692

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.484 AC: 73672 AN: 152150 Hom.: 18105 Cov.: 34 AF XY: 0.482 AC XY: 35863 AN XY: 74386

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.489

Alfa AF: 0.499 Hom.: 44191

Bravo AF: 0.489

Asia WGS AF: 0.548 AC: 1903 AN: 3478

EpiCase AF: 0.502

EpiControl AF: 0.502

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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	-0.87
Cadd	Benign	0.15
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0020
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: rs2275111; hg19: chr10-120917445; COSMIC: COSV57460793; COSMIC: COSV57460793;