rs80335370

Variant names:

• chr11-793588-G-A
• rs80335370
• NM_001191061.2:c.234C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-793588-G-A
• chr11-793588-G-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001425344.1(SLC25A22):​c.-85C>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 0.12 in 1,611,342 control chromosomes in the GnomAD database, including 12,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (762 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11608 hom.)
• Consequence: SLC25A22 NM_001425344.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.35
• Publications: 14 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 11-793588-G-A is Benign according to our data. Variant chr11-793588-G-A is described in ClinVar as Benign. ClinVar VariationId is 159913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

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.234C>T	p.Pro78Pro	synonymous	Exon 5 of 10	NP_001177990.1	Q9H936
	SLC25A22	NM_001425344.1		c.-85C>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 10	NP_001412273.1
	SLC25A22	NM_001425334.1		c.309C>T	p.Pro103Pro	synonymous	Exon 5 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.234C>T	p.Pro78Pro	synonymous	Exon 5 of 10	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000320230.9	TSL:1	c.234C>T	p.Pro78Pro	synonymous	Exon 5 of 10	ENSP00000322020.5	Q9H936
	SLC25A22	ENST00000860087.1		c.309C>T	p.Pro103Pro	synonymous	Exon 5 of 10	ENSP00000530146.1

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14308 AN: 152044 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0784

GnomAD2 exomes AF: 0.0965 AC: 24059 AN: 249224 AF XY: 0.0984

Gnomad AFR exome AF: 0.0420

Gnomad AMR exome AF: 0.0675

Gnomad ASJ exome AF: 0.0626

Gnomad EAS exome AF: 0.0641

Gnomad FIN exome AF: 0.0992

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.0988

GnomAD4 exome AF: 0.122 AC: 178487 AN: 1459180 Hom.: 11608 Cov.: 32 AF XY: 0.121 AC XY: 87839 AN XY: 725874

African (AFR) AF: 0.0394 AC: 1320 AN: 33480

American (AMR) AF: 0.0693 AC: 3098 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 1679 AN: 26136

East Asian (EAS) AF: 0.0675 AC: 2678 AN: 39698

South Asian (SAS) AF: 0.0789 AC: 6803 AN: 86256

European-Finnish (FIN) AF: 0.0996 AC: 5063 AN: 50828

Middle Eastern (MID) AF: 0.0550 AC: 317 AN: 5768

European-Non Finnish (NFE) AF: 0.136 AC: 151063 AN: 1111916

Other (OTH) AF: 0.107 AC: 6466 AN: 60382

GnomAD4 genome AF: 0.0940 AC: 14310 AN: 152162 Hom.: 762 Cov.: 32 AF XY: 0.0915 AC XY: 6809 AN XY: 74386

African (AFR) AF: 0.0444 AC: 1842 AN: 41530

American (AMR) AF: 0.0911 AC: 1393 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.0624 AC: 322 AN: 5162

South Asian (SAS) AF: 0.0817 AC: 393 AN: 4808

European-Finnish (FIN) AF: 0.0925 AC: 981 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8919 AN: 67968

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0908 Hom.: 659

Bravo AF: 0.0898

Asia WGS AF: 0.0940 AC: 324 AN: 3478

EpiCase AF: 0.121

EpiControl AF: 0.123

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Developmental and epileptic encephalopathy (1)
-	-	1	Early myoclonic encephalopathy (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.44
DANN	Benign	0.89
PhyloP100		-2.4
Mutation Taster		=98/2	polymorphism (auto)

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: rs80335370; hg19: chr11-793588; COSMIC: COSV57192934; COSMIC: COSV57192934;