rs1215087087

Variant names:

• chr11-793587-C-G
• rs1215087087
• NM_001191061.2:c.235G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-793587-C-G
• chr11-793587-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• 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: G2P, Labcorp Genetics (formerly Invitae)
• 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: 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

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.235G>C	p.Glu79Gln	missense	Exon 5 of 10	NP_001177990.1	Q9H936
	SLC25A22	NM_001425334.1		c.310G>C	p.Glu104Gln	missense	Exon 5 of 10	NP_001412263.1
	SLC25A22	NM_001425335.1		c.235G>C	p.Glu79Gln	missense	Exon 5 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.235G>C	p.Glu79Gln	missense	Exon 5 of 10	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000320230.9	TSL:1	c.235G>C	p.Glu79Gln	missense	Exon 5 of 10	ENSP00000322020.5	Q9H936
	SLC25A22	ENST00000860087.1		c.310G>C	p.Glu104Gln	missense	Exon 5 of 10	ENSP00000530146.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459454 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726040

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	36
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.7	L
PhyloP100		4.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.034	D
Polyphen		0.99	D
Vest4		0.75
MutPred		0.66		Gain of methylation at K83 (P = 0.1562)
MVP		0.72
MPC		1.2
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.88
gMVP		0.98
Mutation Taster		=10/90	disease causing

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

Other links and lift over

dbSNP: rs1215087087; hg19: chr11-793587;