rs150544061

Variant names:

• chr11-792428-C-T
• rs150544061
• NM_001191061.2:c.618G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001191061.2(SLC25A22):​c.618G>A​(p.Pro206Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,613,360 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (142 hom.)
• Consequence: SLC25A22 NM_001191061.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.89
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 11-792428-C-T is Benign according to our data. Variant chr11-792428-C-T is described in ClinVar as Benign. ClinVar VariationId is 139141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.88 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00271 (412/152252) while in subpopulation SAS AF = 0.0415 (200/4818). AF 95% confidence interval is 0.0368. There are 4 homozygotes in GnomAd4. There are 263 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

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.618G>A	p.Pro206Pro	synonymous	Exon 8 of 10	NP_001177990.1	Q9H936
	SLC25A22	NM_001425334.1		c.693G>A	p.Pro231Pro	synonymous	Exon 8 of 10	NP_001412263.1
	SLC25A22	NM_001425335.1		c.657G>A	p.Pro219Pro	synonymous	Exon 8 of 10	NP_001412264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.618G>A	p.Pro206Pro	synonymous	Exon 8 of 10	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000320230.9	TSL:1	c.618G>A	p.Pro206Pro	synonymous	Exon 8 of 10	ENSP00000322020.5	Q9H936
	SLC25A22	ENST00000860087.1		c.693G>A	p.Pro231Pro	synonymous	Exon 8 of 10	ENSP00000530146.1

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 410 AN: 152134 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00737 AC: 1842 AN: 249908 AF XY: 0.00879

Gnomad AFR exome AF: 0.00192

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0243

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000712

Gnomad OTH exome AF: 0.00508

GnomAD4 exome AF: 0.00324 AC: 4735 AN: 1461108 Hom.: 142 Cov.: 31 AF XY: 0.00428 AC XY: 3109 AN XY: 726862

African (AFR) AF: 0.00170 AC: 57 AN: 33476

American (AMR) AF: 0.000268 AC: 12 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0200 AC: 793 AN: 39694

South Asian (SAS) AF: 0.0403 AC: 3480 AN: 86258

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52768

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111922

Other (OTH) AF: 0.00552 AC: 333 AN: 60378

GnomAD4 genome AF: 0.00271 AC: 412 AN: 152252 Hom.: 4 Cov.: 33 AF XY: 0.00353 AC XY: 263 AN XY: 74430

African (AFR) AF: 0.00188 AC: 78 AN: 41550

American (AMR) AF: 0.000261 AC: 4 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5178

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67998

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.000736 Hom.: 0

Bravo AF: 0.00192

Asia WGS AF: 0.0360 AC: 124 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.4
DANN	Benign	0.79
PhyloP100		-1.9
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: rs150544061; hg19: chr11-792428; COSMIC: COSV107332726; COSMIC: COSV107332726;