dbSNP rs1215087087: SLC25A22:p.Glu79Gln (chr11-793587-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B.

PM2PP3

The NM_001191061.2(SLC25A22):c.235G>C(p.Glu79Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E79K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC25A22
NM_001191061.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
developmental and epileptic encephalopathy, 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
early myoclonic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC25A22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A22	NM_001191061.2 link	c.235G>C	p.Glu79Gln	missense_variant	Exon 5 of 10	ENST00000628067.3	NP_001177990.1	Q9H936

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3 link	c.235G>C	p.Glu79Gln	missense_variant	Exon 5 of 10	1	NM_001191061.2	ENSP00000486058.1		Q9H936

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459454

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000383

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:

51052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111962

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

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

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

1.0

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

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.75

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

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

1.7

L;L;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.

PhyloP100

4.0

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.9

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

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.034

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

Polyphen

0.99

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

Vest4

0.75

MutPred

0.66

Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);.;Gain of methylation at K83 (P = 0.1562);.;Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);Gain of methylation at K83 (P = 0.1562);

MVP

0.72

MPC

1.2

ClinPred

0.99

GERP RS

3.4

Varity_R

0.88

gMVP

0.98

Mutation Taster

=10/90

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: -3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over