Variant chr14-100292390-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039355.3(SLC25A29):c.805G>A(p.Val269Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000849 in 1,413,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

SLC25A29
NM_001039355.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

SLC25A29 (HGNC:20116): (solute carrier family 25 member 29) This gene encodes a nuclear-encoded mitochondrial protein that is a member of the large family of solute carrier family 25 (SLC25) mitochondrial transporters. The members of this superfamily are involved in numerous metabolic pathways and cell functions. This gene product was previously reported to be a mitochondrial carnitine-acylcarnitine-like (CACL) translocase (PMID:128829710) or an ornithine transporter (designated ORNT3, PMID:19287344), however, a recent study characterized the main role of this protein as a mitochondrial transporter of basic amino acids, with a preference for arginine and lysine (PMID:24652292). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

SLC25A29 links:

SLC25A29 (HGNC:):

SLC25A29 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A29	NM_001039355.3 linkuse as main transcript	c.805G>A	p.Val269Ile	missense_variant	4/4	ENST00000359232.8	NP_001034444.1	Q8N8R3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A29	ENST00000359232.8 linkuse as main transcript	c.805G>A	p.Val269Ile	missense_variant	4/4	1	NM_001039355.3	ENSP00000352167.3		Q8N8R3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000849

AC:

AN:

1413074

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

699336

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:

0.0000110

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

The c.805G>A (p.V269I) alteration is located in exon 4 (coding exon 4) of the SLC25A29 gene. This alteration results from a G to A substitution at nucleotide position 805, causing the valine (V) at amino acid position 269 to be replaced by an isoleucine (I). 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

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;.;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;.;.;D

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Uncertain

0.29

MutationAssessor

Uncertain

2.2

M;.;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.80

N;N;N;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Uncertain

0.040

D;T;T;T

Polyphen

1.0

D;.;.;.

Vest4

0.46

MutPred

0.57

Loss of sheet (P = 1e-04);.;.;.;

MVP

0.87

MPC

0.86

ClinPred

0.81

GERP RS

5.6

Varity_R

0.18

gMVP

0.68

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over