11-791939-C-T

Variant names:

• chr11-791939-C-T
• rs1554965239
• NM_001191061.2:c.948G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001191061.2(SLC25A22):​c.948G>A​(p.Gly316Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G316G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC25A22 NM_001191061.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• 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), 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.82 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.948G>A	p.Gly316Gly	synonymous_variant	Exon 10 of 10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067.3	c.948G>A	p.Gly316Gly	synonymous_variant	Exon 10 of 10	1	NM_001191061.2	ENSP00000486058.1
SLC25A22	ENST00000320230.9	c.948G>A	p.Gly316Gly	synonymous_variant	Exon 10 of 10	1		ENSP00000322020.5
SLC25A22	ENST00000531214.5	c.948G>A	p.Gly316Gly	synonymous_variant	Exon 10 of 10	2		ENSP00000437236.1
SLC25A22	ENST00000481290.5	c.*84G>A		downstream_gene_variant		5		ENSP00000431829.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.5
DANN	Benign	0.82
PhyloP100		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1554965239; hg19: chr11-791939;