5-110738249-T-G

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001303250.3(SLC25A46):​c.10+2T>G variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000882 in 1,134,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
Exomes 𝑓: 8.8e-7 ( 0 hom. )

Consequence

SLC25A46
NM_001303250.3 splice_donor, intron

Scores

1
1
Splicing: ADA: 0.5943
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39
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]
TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A46NM_001303250.3 linkc.10+2T>G splice_donor_variant, intron_variant Intron 1 of 7 NP_001290179.1 Q96AG3B4DY98
TMEM232XM_006714670.4 linkc.-298+473A>C intron_variant Intron 1 of 15 XP_006714733.1 C9JQI7-1
TMEM232XM_011543552.3 linkc.-649+473A>C intron_variant Intron 1 of 16 XP_011541854.1 C9JQI7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A46ENST00000513807.5 linkc.-204+2T>G splice_donor_variant, intron_variant Intron 1 of 7 2 ENSP00000421134.1 E7EVY2
TMEM232ENST00000515278.6 linkc.-298+473A>C intron_variant Intron 1 of 6 5 ENSP00000421614.2 D6REY3
TMEM232ENST00000503527.6 linkn.197+473A>C intron_variant Intron 1 of 3 3
SLC25A46ENST00000508781.5 linkn.112+2T>G splice_donor_variant, intron_variant Intron 1 of 7 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000791
AC:
1
AN:
126476
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
69308
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000979
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
8.82e-7
AC:
1
AN:
1134414
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
556450
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000789
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.17
CADD
Benign
18
DANN
Uncertain
0.99

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.59
dbscSNV1_RF
Pathogenic
0.77

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: rs147877745; hg19: chr5-110073950; API