NM_001191061.2:c.464G>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001191061.2(SLC25A22):c.464G>C(p.Gly155Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,559,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G155C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SLC25A22
NM_001191061.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.768

Publications

1 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), PanelApp Australia, 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023228854).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000184 (28/152298) while in subpopulation AFR AF = 0.000602 (25/41558). AF 95% confidence interval is 0.000418. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191061.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A22	NM_001191061.2	MANE Select	c.464G>C	p.Gly155Ala	missense	Exon 7 of 10	NP_001177990.1	Q9H936
SLC25A22	NM_001425334.1		c.539G>C	p.Gly180Ala	missense	Exon 7 of 10	NP_001412263.1
SLC25A22	NM_001425335.1		c.503G>C	p.Gly168Ala	missense	Exon 7 of 10	NP_001412264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.464G>C	p.Gly155Ala	missense	Exon 7 of 10	ENSP00000486058.1	Q9H936
SLC25A22	ENST00000320230.9	TSL:1	c.464G>C	p.Gly155Ala	missense	Exon 7 of 10	ENSP00000322020.5	Q9H936
SLC25A22	ENST00000860087.1		c.539G>C	p.Gly180Ala	missense	Exon 7 of 10	ENSP00000530146.1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000478

GnomAD2 exomes

AF:

0.0000429

AC:

AN:

163258

AF XY:

0.0000225

show subpopulations

Gnomad AFR exome

AF:

0.000661

Gnomad AMR exome

AF:

0.0000384

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:

0.0000142

AC:

AN:

1406818

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

696294

show subpopulations

African (AFR)

AF:

0.000339

AC:

AN:

32412

American (AMR)

AF:

0.0000536

AC:

AN:

37336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25352

East Asian (EAS)

AF:

0.00

AC:

AN:

37142

South Asian (SAS)

AF:

0.00

AC:

AN:

81710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00000368

AC:

AN:

1087346

Other (OTH)

AF:

0.0000513

AC:

AN:

58494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000184

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41558

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.0000310

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.000463

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000344

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Developmental and epileptic encephalopathy (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.30

CADD

Benign

2.0

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.032

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.64

PhyloP100

0.77

PrimateAI

Benign

0.44

PROVEAN

Benign

0.24

REVEL

Benign

0.17

Sift

Benign

0.32

Sift4G

Benign

0.40

Polyphen

0.0010

Vest4

0.15

MVP

0.53

MPC

0.42

ClinPred

0.018

GERP RS

2.5

Varity_R

0.048

gMVP

0.60

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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