11-792861-C-T

Variant names:

• chr11-792861-C-T
• rs369276282
• NM_001191061.2:c.412+9G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001191061.2(SLC25A22):​c.412+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000656 in 1,494,266 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000063 (0 hom.)
• Consequence: SLC25A22 NM_001191061.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.44
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-792861-C-T is Benign according to our data. Variant chr11-792861-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 378592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000633 (85/1342404) while in subpopulation MID AF = 0.00126 (7/5572). AF 95% confidence interval is 0.000589. There are 0 homozygotes in GnomAdExome4. There are 40 alleles in the male GnomAdExome4 subpopulation. Median coverage is 38. 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	NM_001191061.2	MANE Select	c.412+9G>A		intron	N/A	NP_001177990.1	Q9H936
	SLC25A22	NM_001425334.1		c.487+9G>A		intron	N/A	NP_001412263.1
	SLC25A22	NM_001425335.1		c.412+9G>A		intron	N/A	NP_001412264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.412+9G>A		intron	N/A	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000320230.9	TSL:1	c.412+9G>A		intron	N/A	ENSP00000322020.5	Q9H936
	SLC25A22	ENST00000860087.1		c.487+9G>A		intron	N/A	ENSP00000530146.1

Frequencies

GnomAD3 genomes AF: 0.0000923 AC: 14 AN: 151744 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000494 AC: 12 AN: 242880 AF XY: 0.0000605

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000916

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000633 AC: 85 AN: 1342404 Hom.: 0 Cov.: 38 AF XY: 0.0000595 AC XY: 40 AN XY: 672354

African (AFR) AF: 0.000599 AC: 19 AN: 31732

American (AMR) AF: 0.00 AC: 0 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25308

East Asian (EAS) AF: 0.00 AC: 0 AN: 38890

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49674

Middle Eastern (MID) AF: 0.00126 AC: 7 AN: 5572

European-Non Finnish (NFE) AF: 0.0000507 AC: 51 AN: 1006892

Other (OTH) AF: 0.000124 AC: 7 AN: 56500

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151862 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74234

African (AFR) AF: 0.000145 AC: 6 AN: 41450

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67844

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.0000391 Hom.: 0

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	-0.89
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		-2.4
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: rs369276282; hg19: chr11-792861;