10-119140986-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.60
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 -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 GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFXN4NM_213649.2 linkuse as main transcriptc.*256G>A 3_prime_UTR_variant 14/14 ENST00000355697.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFXN4ENST00000355697.7 linkuse as main transcriptc.*256G>A 3_prime_UTR_variant 14/141 NM_213649.2 P1Q6P4A7-1
SFXN4ENST00000484960.5 linkuse as main transcriptn.482G>A non_coding_transcript_exon_variant 3/33
SFXN4ENST00000490417.6 linkuse as main transcriptn.733G>A non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
AF:
0.00306
AC:
466
AN:
152066
Hom.:
2
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 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

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

Other links and lift over

dbSNP: rs115303392; hg19: chr10-120900498; API