22-40779050-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006358.4(SLC25A17):​c.410G>A​(p.Arg137Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC25A17
NM_006358.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
Variant links:
Genes affected
SLC25A17 (HGNC:10987): (solute carrier family 25 member 17) This gene encodes a peroxisomal membrane protein that belongs to the family of mitochondrial solute carriers. It is expressed in the liver, and is likely involved in transport. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22624254).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A17NM_006358.4 linkc.410G>A p.Arg137Lys missense_variant Exon 5 of 9 ENST00000435456.7 NP_006349.1 O43808

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A17ENST00000435456.7 linkc.410G>A p.Arg137Lys missense_variant Exon 5 of 9 1 NM_006358.4 ENSP00000390722.2 O43808

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461838
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727218
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.410G>A (p.R137K) alteration is located in exon 5 (coding exon 5) of the SLC25A17 gene. This alteration results from a G to A substitution at nucleotide position 410, causing the arginine (R) at amino acid position 137 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.069
T;.;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.63
N;.;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.78
N;.;N
REVEL
Uncertain
0.41
Sift
Benign
0.25
T;.;T
Sift4G
Benign
0.77
T;T;T
Polyphen
0.0090
B;.;.
Vest4
0.35
MutPred
0.38
Gain of ubiquitination at R137 (P = 0.0325);.;.;
MVP
0.61
MPC
0.21
ClinPred
0.78
D
GERP RS
5.1
Varity_R
0.23
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1485784044; hg19: chr22-41175054; API