rs113091974

Variant names:

• chr11-792860-C-A
• rs113091974
• NM_001191061.2:c.412+10G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-792860-C-A
• chr11-792860-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001191061.2(SLC25A22):​c.412+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 1,449,026 control chromosomes in the GnomAD database, including 656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (343 hom., cov: 31)
  • Exomes 𝑓: 0.0044 (313 hom.)
• Consequence: SLC25A22 NM_001191061.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.38
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-792860-C-A is Benign according to our data. Variant chr11-792860-C-A is described in ClinVar as Benign. ClinVar VariationId is 159915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

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+10G>T		intron	N/A	NP_001177990.1	Q9H936
	SLC25A22	NM_001425334.1		c.487+10G>T		intron	N/A	NP_001412263.1
	SLC25A22	NM_001425335.1		c.412+10G>T		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+10G>T		intron	N/A	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000320230.9	TSL:1	c.412+10G>T		intron	N/A	ENSP00000322020.5	Q9H936
	SLC25A22	ENST00000860087.1		c.487+10G>T		intron	N/A	ENSP00000530146.1

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5572 AN: 151390 Hom.: 340 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000428

Gnomad OTH AF: 0.0284

GnomAD2 exomes AF: 0.00983 AC: 2383 AN: 242430 AF XY: 0.00738

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.00752

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000403

Gnomad OTH exome AF: 0.00589

GnomAD4 exome AF: 0.00441 AC: 5719 AN: 1297516 Hom.: 313 Cov.: 38 AF XY: 0.00384 AC XY: 2503 AN XY: 651356

African (AFR) AF: 0.144 AC: 4489 AN: 31068

American (AMR) AF: 0.00884 AC: 391 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24922

East Asian (EAS) AF: 0.00 AC: 0 AN: 38570

South Asian (SAS) AF: 0.000363 AC: 30 AN: 82540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49192

Middle Eastern (MID) AF: 0.00892 AC: 49 AN: 5492

European-Non Finnish (NFE) AF: 0.000228 AC: 220 AN: 966452

Other (OTH) AF: 0.00981 AC: 540 AN: 55044

GnomAD4 genome AF: 0.0368 AC: 5576 AN: 151510 Hom.: 343 Cov.: 31 AF XY: 0.0350 AC XY: 2589 AN XY: 74064

African (AFR) AF: 0.127 AC: 5250 AN: 41296

American (AMR) AF: 0.0152 AC: 232 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5134

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10518

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000428 AC: 29 AN: 67748

Other (OTH) AF: 0.0281 AC: 59 AN: 2098

Alfa AF: 0.0165 Hom.: 46

Bravo AF: 0.0422

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Developmental and epileptic encephalopathy (1)
-	-	1	Developmental and epileptic encephalopathy, 3 (1)
-	-	1	Early myoclonic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0020
DANN	Benign	0.66
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs113091974; hg19: chr11-792860;