Variant chr17-81715523-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012140.5(SLC25A10):c.259G>T(p.Asp87Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC25A10
NM_012140.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

SLC25A10 (HGNC:10980): (solute carrier family 25 member 10) This gene encodes a member of a family of proteins that translocate small metabolites across the mitochondrial membrane. The encoded protein exchanges dicarboxylates, such as malate and succinate, for phosphate, sulfate, and other small molecules, thereby providing substrates for metabolic processes including the Krebs cycle and fatty acid synthesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

SLC25A10 links:

ENSG00000262660 (HGNC:):

ENSG00000262660 links:

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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, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A10	NM_012140.5 linkuse as main transcript	c.259G>T	p.Asp87Tyr	missense_variant	3/11	ENST00000350690.10	NP_036272.2	Q9UBX3-1A0A0S2Z382

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A10	ENST00000350690.10 linkuse as main transcript	c.259G>T	p.Asp87Tyr	missense_variant	3/11	1	NM_012140.5	ENSP00000345580.5		Q9UBX3-1
ENSG00000262660	ENST00000571730.1 linkuse as main transcript	c.724G>T	p.Asp242Tyr	missense_variant	7/15	2		ENSP00000461324.1		B4DLN1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250812

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460624

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Oct 03, 2024

The c.259G>T (p.D87Y) alteration is located in exon 3 (coding exon 3) of the SLC25A10 gene. This alteration results from a G to T substitution at nucleotide position 259, causing the aspartic acid (D) at amino acid position 87 to be replaced by a tyrosine (Y). 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

0.44

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

.;.;.;D

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Pathogenic

0.48

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.4

.;.;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-9.0

.;D;D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

.;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.96, 0.91

.;.;D;P

Vest4

0.80

MutPred

0.27

Gain of MoRF binding (P = 0.0494);.;.;.;

MVP

0.86

MPC

0.96

ClinPred

0.98

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.71

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