chr11-792002-G-A

Variant names:

• chr11-792002-G-A
• rs543285265
• NM_001191061.2:c.885C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001191061.2(SLC25A22):​c.885C>T​(p.Ile295Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,608,502 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SLC25A22 NM_001191061.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -0.938
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-792002-G-A is Benign according to our data. Variant chr11-792002-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212199.
• BP7: Synonymous conserved (PhyloP=-0.938 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	NM_001191061.2	MANE Select	c.885C>T	p.Ile295Ile	synonymous	Exon 10 of 10	NP_001177990.1	Q9H936
	SLC25A22	NM_001425334.1		c.960C>T	p.Ile320Ile	synonymous	Exon 10 of 10	NP_001412263.1
	SLC25A22	NM_001425335.1		c.924C>T	p.Ile308Ile	synonymous	Exon 10 of 10	NP_001412264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.885C>T	p.Ile295Ile	synonymous	Exon 10 of 10	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000320230.9	TSL:1	c.885C>T	p.Ile295Ile	synonymous	Exon 10 of 10	ENSP00000322020.5	Q9H936
	SLC25A22	ENST00000860087.1		c.960C>T	p.Ile320Ile	synonymous	Exon 10 of 10	ENSP00000530146.1

Frequencies

GnomAD3 genomes AF: 0.0000525 AC: 8 AN: 152240 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000511 AC: 12 AN: 234716 AF XY: 0.0000389

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000964

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.0000227 AC: 33 AN: 1456144 Hom.: 0 Cov.: 31 AF XY: 0.0000276 AC XY: 20 AN XY: 724220

African (AFR) AF: 0.0000900 AC: 3 AN: 33336

American (AMR) AF: 0.0000226 AC: 1 AN: 44306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39462

South Asian (SAS) AF: 0.000187 AC: 16 AN: 85710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5208

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110328

Other (OTH) AF: 0.0000998 AC: 6 AN: 60110

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152358 Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5 AN XY: 74506

African (AFR) AF: 0.0000481 AC: 2 AN: 41594

American (AMR) AF: 0.000196 AC: 3 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000642

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.3
DANN	Benign	0.86
PhyloP100		-0.94
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs543285265; hg19: chr11-792002;