chr11-794483-G-A

Variant names:

• chr11-794483-G-A
• rs761165876
• NM_001191061.2:c.177C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001425344.1(SLC25A22):​c.-147C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,612,918 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: SLC25A22 NM_001425344.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.73
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 11-794483-G-A is Benign according to our data. Variant chr11-794483-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 380713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425344.1. 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.177C>T	p.Ser59Ser	synonymous	Exon 4 of 10	NP_001177990.1	Q9H936
	SLC25A22	NM_001425344.1		c.-147C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 10	NP_001412273.1
	SLC25A22	NM_001425334.1		c.252C>T	p.Ser84Ser	synonymous	Exon 4 of 10	NP_001412263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.177C>T	p.Ser59Ser	synonymous	Exon 4 of 10	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000320230.9	TSL:1	c.177C>T	p.Ser59Ser	synonymous	Exon 4 of 10	ENSP00000322020.5	Q9H936
	SLC25A22	ENST00000532361.5	TSL:1	n.392C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000846 AC: 21 AN: 248174 AF XY: 0.000111

Gnomad AFR exome AF: 0.0000629

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000984

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 171 AN: 1460718 Hom.: 1 Cov.: 32 AF XY: 0.000110 AC XY: 80 AN XY: 726660

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52580

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5750

European-Non Finnish (NFE) AF: 0.000122 AC: 136 AN: 1111850

Other (OTH) AF: 0.000199 AC: 12 AN: 60368

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74348

African (AFR) AF: 0.0000965 AC: 4 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.000102

EpiCase AF: 0.000382

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.021
DANN	Benign	0.93
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs761165876; hg19: chr11-794483; COSMIC: COSV57195535; COSMIC: COSV57195535;