rs77117049

Variant names:

• chr11-792579-G-A
• rs77117049
• NM_001191061.2:c.561C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-792579-G-A
• chr11-792579-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001425334.1(SLC25A22):​c.636C>T​(p.Tyr212Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00701 in 1,612,022 control chromosomes in the GnomAD database, including 661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (354 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (307 hom.)
• Consequence: SLC25A22 NM_001425334.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.57
• 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), 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-792579-G-A is Benign according to our data. Variant chr11-792579-G-A is described in ClinVar as Benign. ClinVar VariationId is 159917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.
• 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_001425334.1. 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.561C>T	p.Tyr187Tyr	synonymous	Exon 7 of 10	NP_001177990.1
	SLC25A22	NM_001425334.1		c.636C>T	p.Tyr212Tyr	synonymous	Exon 7 of 10	NP_001412263.1
	SLC25A22	NM_001425335.1		c.600C>T	p.Tyr200Tyr	synonymous	Exon 7 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.561C>T	p.Tyr187Tyr	synonymous	Exon 7 of 10	ENSP00000486058.1
	SLC25A22	ENST00000320230.9	TSL:1	c.561C>T	p.Tyr187Tyr	synonymous	Exon 7 of 10	ENSP00000322020.5
	SLC25A22	ENST00000937625.1		c.553C>T	p.Gln185*	stop_gained	Exon 7 of 10	ENSP00000607684.1

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5602 AN: 152028 Hom.: 350 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.00943 AC: 2295 AN: 243288 AF XY: 0.00721

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.00738

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000387

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00390 AC: 5696 AN: 1459876 Hom.: 307 Cov.: 32 AF XY: 0.00343 AC XY: 2493 AN XY: 726258

African (AFR) AF: 0.134 AC: 4472 AN: 33470

American (AMR) AF: 0.00865 AC: 386 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51936

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5766

European-Non Finnish (NFE) AF: 0.000201 AC: 224 AN: 1111750

Other (OTH) AF: 0.00890 AC: 537 AN: 60338

GnomAD4 genome AF: 0.0369 AC: 5607 AN: 152146 Hom.: 354 Cov.: 33 AF XY: 0.0350 AC XY: 2600 AN XY: 74366

African (AFR) AF: 0.127 AC: 5281 AN: 41500

American (AMR) AF: 0.0151 AC: 231 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67970

Other (OTH) AF: 0.0289 AC: 61 AN: 2112

Alfa AF: 0.0118 Hom.: 31

Bravo AF: 0.0424

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	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	-0.55
CADD	Benign	7.5
DANN	Benign	0.80
PhyloP100		1.6
Mutation Taster		=100/0	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: rs77117049; hg19: chr11-792579;