11-791009-C-T

Position:

• chr11-791009-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001191061.2(SLC25A22):​c.*906G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,308 control chromosomes in the GnomAD database, including 750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (749 hom., cov: 33)
  • Exomes 𝑓: 0.080 (1 hom.)
• Consequence: SLC25A22 NM_001191061.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.47

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-791009-C-T is Benign according to our data. Variant chr11-791009-C-T is described in ClinVar as [Benign]. Clinvar id is 306239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.*906G>A		3_prime_UTR_variant	10/10	ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A22	ENST00000628067	c.*906G>A		3_prime_UTR_variant	10/10	1	NM_001191061.2	ENSP00000486058.1
SLC25A22	ENST00000320230	c.*906G>A		3_prime_UTR_variant	10/10	1		ENSP00000322020.5

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13660 AN: 152104 Hom.: 750 Cov.: 33

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0806

GnomAD4 exome AF: 0.0795 AC: 7 AN: 88 Hom.: 1 Cov.: 0 AF XY: 0.0500 AC XY: 3 AN XY: 60

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.0484

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0897 AC: 13661 AN: 152220 Hom.: 749 Cov.: 33 AF XY: 0.0872 AC XY: 6487 AN XY: 74412

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.0935

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.0623

Gnomad4 SAS AF: 0.0828

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0845

Alfa AF: 0.110 Hom.: 139

Bravo AF: 0.0849

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Early myoclonic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs118051043; hg19: chr11-791009;