rs2297696

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000355697.7(SFXN4):​c.538-199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,840 control chromosomes in the GnomAD database, including 7,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7562 hom., cov: 31)

Consequence

SFXN4
ENST00000355697.7 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.347
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 10-119156955-A-G is Benign according to our data. Variant chr10-119156955-A-G is described in ClinVar as [Benign]. Clinvar id is 667486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SFXN4NM_213649.2 linkuse as main transcriptc.538-199T>C intron_variant ENST00000355697.7 NP_998814.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SFXN4ENST00000355697.7 linkuse as main transcriptc.538-199T>C intron_variant 1 NM_213649.2 ENSP00000347924 P1Q6P4A7-1
SFXN4ENST00000369131.8 linkuse as main transcriptc.190-199T>C intron_variant 5 ENSP00000358127
SFXN4ENST00000461438.5 linkuse as main transcriptn.567-199T>C intron_variant, non_coding_transcript_variant 5
SFXN4ENST00000466218.5 linkuse as main transcriptn.487-199T>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.299
AC:
45406
AN:
151722
Hom.:
7566
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.163
Gnomad AMI
AF:
0.405
Gnomad AMR
AF:
0.285
Gnomad ASJ
AF:
0.304
Gnomad EAS
AF:
0.170
Gnomad SAS
AF:
0.391
Gnomad FIN
AF:
0.458
Gnomad MID
AF:
0.266
Gnomad NFE
AF:
0.362
Gnomad OTH
AF:
0.308
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.299
AC:
45401
AN:
151840
Hom.:
7562
Cov.:
31
AF XY:
0.304
AC XY:
22547
AN XY:
74154
show subpopulations
Gnomad4 AFR
AF:
0.163
Gnomad4 AMR
AF:
0.285
Gnomad4 ASJ
AF:
0.304
Gnomad4 EAS
AF:
0.169
Gnomad4 SAS
AF:
0.390
Gnomad4 FIN
AF:
0.458
Gnomad4 NFE
AF:
0.362
Gnomad4 OTH
AF:
0.309
Alfa
AF:
0.345
Hom.:
18714
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
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
5.9
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2297696; hg19: chr10-120916467; API