Genetic Variant NM_001191061.2:c.495C>T (chr11-792645-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_001191061.2(SLC25A22):c.495C>T(p.Ala165Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000663 in 1,581,150 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 1 hom. )

Consequence

SLC25A22
NM_001191061.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:7

Conservation

PhyloP100: -1.17

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-792645-G-A is Benign according to our data. Variant chr11-792645-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 139138.

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000578 (88/152312) while in subpopulation AMR AF = 0.00176 (27/15308). AF 95% confidence interval is 0.00124. There are 0 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.495C>T	p.Ala165Ala	synonymous	Exon 7 of 10	NP_001177990.1	Q9H936
SLC25A22	NM_001425334.1		c.570C>T	p.Ala190Ala	synonymous	Exon 7 of 10	NP_001412263.1
SLC25A22	NM_001425335.1		c.534C>T	p.Ala178Ala	synonymous	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.495C>T	p.Ala165Ala	synonymous	Exon 7 of 10	ENSP00000486058.1	Q9H936
SLC25A22	ENST00000320230.9	TSL:1	c.495C>T	p.Ala165Ala	synonymous	Exon 7 of 10	ENSP00000322020.5	Q9H936
SLC25A22	ENST00000937625.1		c.487C>T	p.Pro163Ser	missense	Exon 7 of 10	ENSP00000607684.1

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000690

AC:

131

AN:

189856

AF XY:

0.000768

show subpopulations

Gnomad AFR exome

AF:

0.0000930

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.000668

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000215

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.000799

GnomAD4 exome

AF:

0.000672

AC:

960

AN:

1428838

Hom.:

Cov.:

AF XY:

0.000676

AC XY:

479

AN XY:

708720

show subpopulations

African (AFR)

AF:

0.0000910

AC:

AN:

32956

American (AMR)

AF:

0.00142

AC:

AN:

40082

Ashkenazi Jewish (ASJ)

AF:

0.000546

AC:

AN:

25630

East Asian (EAS)

AF:

0.00

AC:

AN:

38266

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83502

European-Finnish (FIN)

AF:

0.0000433

AC:

AN:

46176

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.000772

AC:

847

AN:

1097288

Other (OTH)

AF:

0.000574

AC:

AN:

59214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.000578

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41564

American (AMR)

AF:

0.00176

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000967

Hom.:

Bravo

AF:

0.000820

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Developmental and epileptic encephalopathy (1)

Early myoclonic encephalopathy (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.93

(source)

DANN

Benign

0.63

PhyloP100

-1.2

Mutation Taster

=100/0

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