rs1554091122

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_138773.4(SLC25A46):​c.134C>G​(p.Thr45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC25A46
NM_138773.4 missense

Scores

2
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.96
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a modified_residue Phosphothreonine (size 0) in uniprot entity S2546_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19482982).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC25A46NM_138773.4 linkuse as main transcriptc.134C>G p.Thr45Ser missense_variant 1/8 ENST00000355943.8 NP_620128.1
SLC25A46NM_001303249.3 linkuse as main transcriptc.134C>G p.Thr45Ser missense_variant 1/8 NP_001290178.1
SLC25A46NM_001303250.3 linkuse as main transcriptc.10+1006C>G intron_variant NP_001290179.1
SLC25A46NR_138151.2 linkuse as main transcriptn.247C>G non_coding_transcript_exon_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC25A46ENST00000355943.8 linkuse as main transcriptc.134C>G p.Thr45Ser missense_variant 1/81 NM_138773.4 ENSP00000348211 P1Q96AG3-1
SLC25A46ENST00000447245.6 linkuse as main transcriptc.134C>G p.Thr45Ser missense_variant 1/82 ENSP00000399717 Q96AG3-3
SLC25A46ENST00000513807.5 linkuse as main transcriptc.-204+1006C>G intron_variant 2 ENSP00000421134
SLC25A46ENST00000508781.5 linkuse as main transcriptn.112+1006C>G intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.010
T;.
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.057
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.71
T;T
M_CAP
Pathogenic
0.37
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.32
T
MutationAssessor
Benign
1.6
L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.56
N;N
REVEL
Uncertain
0.30
Sift
Benign
0.17
T;T
Sift4G
Benign
0.24
T;T
Polyphen
0.0070
B;.
Vest4
0.14
MutPred
0.16
Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP
0.62
MPC
0.052
ClinPred
0.63
D
GERP RS
3.3
Varity_R
0.15
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1554091122; hg19: chr5-110074954; API