Genetic Variant SLC22A25:p.Gly479Glu (chr11-63164032-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_199352.6(SLC22A25):c.1436G>A(p.Gly479Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,610,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SLC22A25
NM_199352.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.739

Publications

0 publications found

Variant links:

Genes affected

SLC22A25 (HGNC:32935): (solute carrier family 22 member 25) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC22A25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A25	NM_199352.6 link	c.1436G>A	p.Gly479Glu	missense_variant	Exon 12 of 12	ENST00000306494.11	NP_955384.3	Q6T423

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11 link	c.1436G>A	p.Gly479Glu	missense_variant	Exon 12 of 12	1	NM_199352.6	ENSP00000307443.6		Q6T423

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000323

AC:

AN:

247480

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.0000295

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:

0.00000754

AC:

AN:

1458426

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725250

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33336

American (AMR)

AF:

0.0000226

AC:

AN:

44242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25924

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

85628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110290

Other (OTH)

AF:

0.0000166

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41414

American (AMR)

AF:

0.000197

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1436G>A (p.G479E) alteration is located in exon 9 (coding exon 9) of the SLC22A25 gene. This alteration results from a G to A substitution at nucleotide position 1436, causing the glycine (G) at amino acid position 479 to be replaced by a glutamic acid (E). 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

0.75

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.35

M_CAP

Benign

0.0046

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.35

MutationAssessor

Pathogenic

3.8

PhyloP100

0.74

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-6.6

REVEL

Uncertain

0.33

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0010

Polyphen

0.98

Vest4

0.64

MVP

0.48

MPC

0.11

ClinPred

0.77

GERP RS

3.1

Varity_R

0.93

gMVP

0.86

Mutation Taster

=100/0

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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11-63164032-C-T

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