chr11-798081-A-G

Variant names:

• chr11-798081-A-G
• rs531366837
• ENST00000678030.1:c.456A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The ENST00000678030.1(PANO1):​c.456A>G​(p.Gly152Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 394,222 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G152G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00053 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: PANO1 ENST00000678030.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 0 publications found

Genes affected

PANO1 (HGNC:51237): (proapoptotic nucleolar protein 1) Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of apoptotic process; and regulation of protein stability. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000678030.1. 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.-164+136T>C		intron	N/A	NP_001177990.1	Q9H936
	SLC25A22	NM_001425334.1		c.-164+136T>C		intron	N/A	NP_001412263.1
	SLC25A22	NM_001425335.1		c.-164+136T>C		intron	N/A	NP_001412264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANO1	ENST00000678030.1		c.456A>G	p.Gly152Gly	synonymous	Exon 1 of 1	ENSP00000503591.1	I0J062
	SLC25A22	ENST00000628067.3	TSL:1 MANE Select	c.-164+136T>C		intron	N/A	ENSP00000486058.1	Q9H936
	SLC25A22	ENST00000860088.1		c.-262T>C		5_prime_UTR	Exon 1 of 10	ENSP00000530147.1

Frequencies

GnomAD3 genomes AF: 0.000532 AC: 79 AN: 148436 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.000644

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000493

GnomAD4 exome AF: 0.000313 AC: 77 AN: 245688 Hom.: 1 Cov.: 0 AF XY: 0.000289 AC XY: 36 AN XY: 124548

African (AFR) AF: 0.00 AC: 0 AN: 7160

American (AMR) AF: 0.00 AC: 0 AN: 7422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9210

East Asian (EAS) AF: 0.00311 AC: 71 AN: 22864

South Asian (SAS) AF: 0.00 AC: 0 AN: 3022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 157618

Other (OTH) AF: 0.000367 AC: 6 AN: 16328

GnomAD4 genome AF: 0.000525 AC: 78 AN: 148534 Hom.: 2 Cov.: 33 AF XY: 0.000483 AC XY: 35 AN XY: 72430

African (AFR) AF: 0.00 AC: 0 AN: 40304

American (AMR) AF: 0.000133 AC: 2 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.0144 AC: 72 AN: 4996

South Asian (SAS) AF: 0.000645 AC: 3 AN: 4648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66896

Other (OTH) AF: 0.000488 AC: 1 AN: 2050

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.51
PhyloP100		-2.0
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs531366837; hg19: chr11-798081;