rs202123515
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_138773.4(SLC25A46):c.416C>A(p.Thr139Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000879 in 1,589,750 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00092 ( 8 hom. )
Consequence
SLC25A46
NM_138773.4 missense
NM_138773.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 7.14
Genes affected
SLC25A46 (HGNC:25198): (solute carrier family 25 member 46) This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.026061535).
BP6
Variant 5-110746300-C-A is Benign according to our data. Variant chr5-110746300-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 475795.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2}.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000922 (1325/1437454) while in subpopulation MID AF= 0.00508 (29/5706). AF 95% confidence interval is 0.00416. There are 8 homozygotes in gnomad4_exome. There are 783 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC25A46 | NM_138773.4 | c.416C>A | p.Thr139Asn | missense_variant | 4/8 | ENST00000355943.8 | NP_620128.1 | |
SLC25A46 | NM_001303249.3 | c.416C>A | p.Thr139Asn | missense_variant | 4/8 | NP_001290178.1 | ||
SLC25A46 | NM_001303250.3 | c.143C>A | p.Thr48Asn | missense_variant | 4/8 | NP_001290179.1 | ||
SLC25A46 | NR_138151.2 | n.529C>A | non_coding_transcript_exon_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC25A46 | ENST00000355943.8 | c.416C>A | p.Thr139Asn | missense_variant | 4/8 | 1 | NM_138773.4 | ENSP00000348211.3 |
Frequencies
GnomAD3 genomes AF: 0.000467 AC: 71AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
71
AN:
152178
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000843 AC: 191AN: 226474Hom.: 1 AF XY: 0.00110 AC XY: 135AN XY: 123176
GnomAD3 exomes
AF:
AC:
191
AN:
226474
Hom.:
AF XY:
AC XY:
135
AN XY:
123176
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000922 AC: 1325AN: 1437454Hom.: 8 Cov.: 28 AF XY: 0.00109 AC XY: 783AN XY: 715154
GnomAD4 exome
AF:
AC:
1325
AN:
1437454
Hom.:
Cov.:
28
AF XY:
AC XY:
783
AN XY:
715154
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000473 AC: 72AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74470
GnomAD4 genome
AF:
AC:
72
AN:
152296
Hom.:
Cov.:
32
AF XY:
AC XY:
34
AN XY:
74470
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
3
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
3
ExAC
AF:
AC:
118
Asia WGS
AF:
AC:
5
AN:
3470
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:4Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 16, 2021 | - - |
Neuropathy, hereditary motor and sensory, type 6B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 02, 2024 | - - |
SLC25A46-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 28, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at