Variant rs1386206620 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001191061.2(SLC25A22):c.85A>T(p.Ile29Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000567 in 1,588,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SLC25A22
NM_001191061.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

SLC25A22 (HGNC:19954): (solute carrier family 25 member 22) This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jul 2010]

SLC25A22 links:

SLC25A22 (HGNC:):

SLC25A22 links:

Genome browser will be placed here

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
SLC25A22	NM_001191061.2 linkuse as main transcript	c.85A>T	p.Ile29Phe	missense_variant	3/10	ENST00000628067.3	NP_001177990.1	Q9H936

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3 linkuse as main transcript	c.85A>T	p.Ile29Phe	missense_variant	3/10	1	NM_001191061.2	ENSP00000486058.1		Q9H936

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000975

AC:

AN:

205078

Hom.:

AF XY:

0.00

AC XY:

AN XY:

109918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000384

GnomAD4 exome

AF:

0.00000348

AC:

AN:

1435882

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711578

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000182

Gnomad4 OTH exome

AF:

0.0000504

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 04, 2022

This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 29 of the SLC25A22 protein (p.Ile29Phe). This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with SLC25A22-related conditions. ClinVar contains an entry for this variant (Variation ID: 461380). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;T;T;.;.;.;.;.;.;.;.;T;T;T;.;.;.;.;.

Eigen

Benign

0.079

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

.;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.56

N;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.1

D;.;D;D;.;D;.;D;D;D;D;D;D;.;D;D;.;D;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.0020

D;.;D;D;.;D;.;D;D;D;D;D;D;.;D;D;.;D;D

Sift4G

Benign

0.11

T;T;T;T;T;.;T;T;D;.;D;.;.;.;.;.;.;.;.

Polyphen

1.0

D;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.80

MutPred

0.57

Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);Gain of catalytic residue at I29 (P = 0.1601);

MVP

0.66

MPC

1.5

ClinPred

0.95

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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