1-15738123-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_207348.3(SLC25A34):​c.475C>T​(p.Arg159Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,604,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R159Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SLC25A34
NM_207348.3 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.296
Variant links:
Genes affected
SLC25A34 (HGNC:27653): (solute carrier family 25 member 34) SLC25A34 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A34NM_207348.3 linkc.475C>T p.Arg159Trp missense_variant Exon 3 of 5 ENST00000294454.6 NP_997231.1 Q6PIV7
SLC25A34XM_017001083.2 linkc.475C>T p.Arg159Trp missense_variant Exon 3 of 4 XP_016856572.1
SLC25A34XM_011541293.2 linkc.475C>T p.Arg159Trp missense_variant Exon 3 of 5 XP_011539595.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A34ENST00000294454.6 linkc.475C>T p.Arg159Trp missense_variant Exon 3 of 5 1 NM_207348.3 ENSP00000294454.5 Q6PIV7
SLC25A34ENST00000489568.1 linkn.243C>T non_coding_transcript_exon_variant Exon 2 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152090
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000854
AC:
21
AN:
245810
Hom.:
0
AF XY:
0.0000753
AC XY:
10
AN XY:
132842
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.0000294
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000237
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000992
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000123
AC:
178
AN:
1452432
Hom.:
0
Cov.:
32
AF XY:
0.000122
AC XY:
88
AN XY:
721158
show subpopulations
Gnomad4 AFR exome
AF:
0.0000600
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000199
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000138
Gnomad4 OTH exome
AF:
0.0000834
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152090
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000674
Hom.:
0
Bravo
AF:
0.0000718
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000124
AC:
15

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.475C>T (p.R159W) alteration is located in exon 3 (coding exon 3) of the SLC25A34 gene. This alteration results from a C to T substitution at nucleotide position 475, causing the arginine (R) at amino acid position 159 to be replaced by a tryptophan (W). 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
0.17
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.61
D
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.87
D
M_CAP
Pathogenic
0.33
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
0.52
D
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.012
D
Polyphen
1.0
D
Vest4
0.74
MVP
0.77
MPC
0.34
ClinPred
0.72
D
GERP RS
4.4
Varity_R
0.23
gMVP
0.75

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: rs139368754; hg19: chr1-16064618; COSMIC: COSV53818040; COSMIC: COSV53818040; API