11-798081-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The ENST00000678030.1(PANO1):​c.456A>C​(p.Gly152Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PANO1 ENST00000678030.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-798081-A-C is Benign according to our data. Variant chr11-798081-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3771377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.

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>G		intron	N/A	NP_001177990.1	Q9H936
	SLC25A22	NM_001425334.1		c.-164+136T>G		intron	N/A	NP_001412263.1
	SLC25A22	NM_001425335.1		c.-164+136T>G		intron	N/A	NP_001412264.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0000404 AC: 6 AN: 148424 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000666

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000100

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000448

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 245686 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124546

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: 0.00 AC: 0 AN: 22864

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20770

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

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

Other (OTH) AF: 0.00 AC: 0 AN: 16328

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000404 AC: 6 AN: 148522 Hom.: 0 Cov.: 33 AF XY: 0.0000276 AC XY: 2 AN XY: 72422

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000248 AC: 1 AN: 40302

American (AMR) AF: 0.0000665 AC: 1 AN: 15038

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4996

South Asian (SAS) AF: 0.00 AC: 0 AN: 4646

European-Finnish (FIN) AF: 0.000100 AC: 1 AN: 9974

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

European-Non Finnish (NFE) AF: 0.0000448 AC: 3 AN: 66890

Other (OTH) AF: 0.00 AC: 0 AN: 2050

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000000277556), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.45
PhyloP100		-2.0
PromoterAI		0.19	Neutral

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;