rs199640801

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001636.4(SLC25A6):ā€‹c.453G>Cā€‹(p.Glu151Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 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)
Exomes š‘“: 0.000021 ( 0 hom. 14 hem. )

Consequence

SLC25A6
NM_001636.4 missense

Scores

1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.877
Variant links:
Genes affected
SLC25A6 (HGNC:10992): (solute carrier family 25 member 6) This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein is implicated in the function of the permability transition pore complex (PTPC), which regulates the release of mitochondrial products that induce apoptosis. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Jun 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11429012).
BS2
High Hemizygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A6NM_001636.4 linkc.453G>C p.Glu151Asp missense_variant Exon 2 of 4 ENST00000381401.11 NP_001627.2 P12236Q6I9V5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A6ENST00000381401.11 linkc.453G>C p.Glu151Asp missense_variant Exon 2 of 4 1 NM_001636.4 ENSP00000370808.5 P12236
SLC25A6ENST00000475167.6 linkn.646G>C non_coding_transcript_exon_variant Exon 3 of 4 2
SLC25A6ENST00000484026.6 linkn.634G>C non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251170
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461414
Hom.:
0
Cov.:
33
AF XY:
0.0000193
AC XY:
14
AN XY:
726994
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:
0.0000270
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_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
9.7
DANN
Benign
0.84
DEOGEN2
Benign
0.25
T
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.86
D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.97
T
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.13
Sift
Benign
0.47
T
Sift4G
Benign
0.21
T
Polyphen
0.0
B
Vest4
0.28
MutPred
0.19
Loss of ubiquitination at K147 (P = 0.1828);
MVP
0.64
MPC
0.45
ClinPred
0.097
T
GERP RS
-0.19
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.071

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: rs199640801; hg19: chrX-1508279; API