3-66262051-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001379210.1(SLC25A26):​c.301G>T​(p.Val101Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000658 in 151,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

SLC25A26
NM_001379210.1 missense, splice_region

Scores

2
11
5
Splicing: ADA: 0.9393
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.60
Variant links:
Genes affected
SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A26NM_001379210.1 linkc.301G>T p.Val101Phe missense_variant, splice_region_variant Exon 4 of 10 ENST00000354883.11 NP_001366139.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A26ENST00000354883.11 linkc.301G>T p.Val101Phe missense_variant, splice_region_variant Exon 4 of 10 2 NM_001379210.1 ENSP00000346955.6 Q70HW3-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151888
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000285
AC:
4
AN:
1405808
Hom.:
1
Cov.:
26
AF XY:
0.00000287
AC XY:
2
AN XY:
696308
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000370
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151888
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74162
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000354
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000827
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.52
D;.;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.81
D;D;D
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
1.8
L;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.1
D;D;.
REVEL
Uncertain
0.58
Sift
Uncertain
0.012
D;T;.
Sift4G
Benign
0.12
T;T;T
Polyphen
0.067
B;.;.
Vest4
0.81
MVP
0.45
MPC
0.039
ClinPred
0.91
D
GERP RS
3.2
Varity_R
0.34
gMVP
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.94
dbscSNV1_RF
Pathogenic
0.72
SpliceAI score (max)
0.050
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: rs774532404; hg19: chr3-66312475; API