rs764360918

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_207348.3(SLC25A34):​c.565G>A​(p.Ala189Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,603,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SLC25A34
NM_207348.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.270
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.009014398).
BP6
Variant 1-15738213-G-A is Benign according to our data. Variant chr1-15738213-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2524230.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A34NM_207348.3 linkc.565G>A p.Ala189Thr missense_variant Exon 3 of 5 ENST00000294454.6 NP_997231.1 Q6PIV7
SLC25A34XM_017001083.2 linkc.565G>A p.Ala189Thr missense_variant Exon 3 of 4 XP_016856572.1
SLC25A34XM_011541293.2 linkc.565G>A p.Ala189Thr 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.565G>A p.Ala189Thr missense_variant Exon 3 of 5 1 NM_207348.3 ENSP00000294454.5 Q6PIV7
SLC25A34ENST00000489568.1 linkn.333G>A non_coding_transcript_exon_variant Exon 2 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.0220
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000125
AC:
3
AN:
239362
Hom.:
0
AF XY:
0.00000772
AC XY:
1
AN XY:
129592
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000550
Gnomad SAS exome
AF:
0.0000350
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000927
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000551
AC:
8
AN:
1451320
Hom.:
0
Cov.:
32
AF XY:
0.00000277
AC XY:
2
AN XY:
721314
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000236
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000452
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152222
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000204
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 25, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
10
DANN
Benign
0.72
DEOGEN2
Benign
0.065
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.0090
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.67
N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.23
Sift
Benign
0.42
T
Sift4G
Benign
0.40
T
Polyphen
0.0030
B
Vest4
0.25
MutPred
0.51
Loss of MoRF binding (P = 0.1193);
MVP
0.10
MPC
0.057
ClinPred
0.011
T
GERP RS
-2.1
Varity_R
0.029
gMVP
0.35

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: rs764360918; hg19: chr1-16064708; COSMIC: COSV99606596; COSMIC: COSV99606596; API