Variant chr17-81712452-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012140.5(SLC25A10):c.26G>A(p.Arg9His) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,310,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SLC25A10
NM_012140.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53

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 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
SLC25A10	NM_012140.5 link	c.26G>A	p.Arg9His	missense_variant	1/11	ENST00000350690.10	NP_036272.2	Q9UBX3-1A0A0S2Z382
SLC25A10	NM_001270953.2 link	c.26G>A	p.Arg9His	missense_variant	1/11		NP_001257882.1	Q9UBX3F6RGN5
SLC25A10	NM_001270888.2 link	c.26G>A	p.Arg9His	missense_variant	1/11		NP_001257817.1	Q9UBX3-2A0A0S2Z3G3
SLC25A10	XM_047435431.1 link	c.26G>A	p.Arg9His	missense_variant	1/10		XP_047291387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A10	ENST00000350690.10 link	c.26G>A	p.Arg9His	missense_variant	1/11	1	NM_012140.5	ENSP00000345580.5		Q9UBX3-1
ENSG00000262660	ENST00000571730.1 link	c.571-2513G>A		intron_variant		2		ENSP00000461324.1		B4DLN1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1158404

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

563202

show subpopulations

Gnomad4 AFR exome

AF:

0.000505

Gnomad4 AMR exome

AF:

0.000254

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:

0.0000431

GnomAD4 genome

AF:

0.000158

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000144

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000292

AC:

AN:

3438

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

Sep 20, 2024

The c.26G>A (p.R9H) alteration is located in exon 1 (coding exon 1) of the SLC25A10 gene. This alteration results from a G to A substitution at nucleotide position 26, causing the arginine (R) at amino acid position 9 to be replaced by a histidine (H). 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

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

.;.;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Pathogenic

0.92

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Uncertain

-0.085

MutationAssessor

Benign

1.6

.;L;L

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.3

.;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.019

.;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.95, 0.85

.;P;P

Vest4

0.42

MutPred

0.63

Loss of MoRF binding (P = 0.0068);Loss of MoRF binding (P = 0.0068);Loss of MoRF binding (P = 0.0068);

MVP

0.79

MPC

1.2

ClinPred

0.99

GERP RS

3.4

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Varity_R

0.40

gMVP

0.14

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.

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