dbSNP rs770294785: SLC25A39:p.Ala261Thr (chr17-44320642-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001143780.3(SLC25A39):c.781G>A(p.Ala261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SLC25A39
NM_001143780.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Publications

0 publications found

Variant links:

Genes affected

SLC25A39 (HGNC:24279): (solute carrier family 25 member 39) This gene encodes a member of the SLC25 transporter or mitochondrial carrier family of proteins. Members of this family are encoded by the nuclear genome while their protein products are usually embedded in the inner mitochondrial membrane and exhibit wide-ranging substrate specificity. Although the encoded protein is currently considered an orphan transporter, this protein is related to other carriers known to transport amino acids. This protein may play a role in iron homeostasis. [provided by RefSeq, Mar 2016]

SLC25A39 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A39	NM_001143780.3 link	c.781G>A	p.Ala261Thr	missense_variant	Exon 9 of 12	ENST00000377095.10	NP_001137252.1	Q9BZJ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A39	ENST00000377095.10 link	c.781G>A	p.Ala261Thr	missense_variant	Exon 9 of 12	1	NM_001143780.3	ENSP00000366299.4		Q9BZJ4-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251386

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000958

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111982

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.000196

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.781G>A (p.A261T) alteration is located in exon 9 (coding exon 8) of the SLC25A39 gene. This alteration results from a G to A substitution at nucleotide position 781, causing the alanine (A) at amino acid position 261 to be replaced by a threonine (T). 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

0.43

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T;.;.;.;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

.;D;D;D;D;D

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.55

D;D;D;D;D;D

MetaSVM

Uncertain

0.27

MutationAssessor

Uncertain

2.8

.;M;.;.;.;.

PhyloP100

1.7

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

N;N;.;.;N;.

REVEL

Uncertain

0.55

Sift

Benign

0.040

D;D;.;.;D;.

Sift4G

Uncertain

0.020

D;D;D;D;D;D

Polyphen

0.69

P;D;P;.;P;.

Vest4

0.64

MutPred

0.74

.;Loss of catalytic residue at M257 (P = 0.0497);.;.;.;.;

MVP

0.83

MPC

0.18

ClinPred

0.37

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.69

Mutation Taster

=60/40

polymorphism

(source)

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

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rs770294785

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over