rs114621664

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001270953.2(SLC25A10):c.574C>T(p.Pro192Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,612,100 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 8 hom. )

Consequence

SLC25A10
NM_001270953.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -0.600

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

mitochondrial DNA depletion syndrome 19
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
mitochondrial disease
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SLC25A10 links:

ENSG00000262660 (HGNC:):

ENSG00000262660 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071317554).

BP6

Variant 17-81717813-C-T is Benign according to our data. Variant chr17-81717813-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 446183.

BS2

High Homozygotes in GnomAdExome4 at 8 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270953.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A10	NM_012140.5	MANE Select	c.657C>T	p.Pro219Pro	synonymous	Exon 9 of 11	NP_036272.2
SLC25A10	NM_001270953.2		c.574C>T	p.Pro192Ser	missense	Exon 9 of 11	NP_001257882.1	F6RGN5
SLC25A10	NM_001270888.2		c.684C>T	p.Pro228Pro	synonymous	Exon 9 of 11	NP_001257817.1	Q9UBX3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A10	ENST00000545862.5	TSL:1	c.574C>T	p.Pro192Ser	missense	Exon 9 of 11	ENSP00000446242.2	F6RGN5
SLC25A10	ENST00000350690.10	TSL:1 MANE Select	c.657C>T	p.Pro219Pro	synonymous	Exon 9 of 11	ENSP00000345580.5	Q9UBX3-1
ENSG00000262660	ENST00000571730.1	TSL:2	c.1122C>T	p.Pro374Pro	synonymous	Exon 13 of 15	ENSP00000461324.1	B4DLN1

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.00126

AC:

313

AN:

248244

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.000880

Gnomad AMR exome

AF:

0.00209

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000975

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.000774

AC:

1130

AN:

1459788

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

580

AN XY:

726132

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

33438

American (AMR)

AF:

0.00269

AC:

120

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00199

AC:

171

AN:

86050

European-Finnish (FIN)

AF:

0.000172

AC:

AN:

52276

Middle Eastern (MID)

AF:

0.00978

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.000500

AC:

556

AN:

1111684

Other (OTH)

AF:

0.00182

AC:

110

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000991

AC:

151

AN:

152312

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41576

American (AMR)

AF:

0.00340

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68004

Other (OTH)

AF:

0.00332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000919

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00120

AC:

146

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

6.3

(source)

DANN

Benign

0.67

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0071

PhyloP100

-0.60

PrimateAI

Benign

0.25

Sift4G

Benign

0.19

Vest4

0.19

MVP

0.62

GERP RS

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.36

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over