chr11-798081-A-AC

Position:

• chr11-798081-A-AC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000678030.1(PANO1):​c.463dup​(p.Leu155ProfsTer170) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 394,212 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: PANO1 ENST00000678030.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-798081-A-AC is Benign according to our data. Variant chr11-798081-A-AC is described in ClinVar as [Benign]. Clinvar id is 1686329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PANO1	XM_034751809.2	c.463dup	p.Leu155ProfsTer170	frameshift_variant	1/1
SLC25A22	NM_001191061.2	c.-164+135_-164+136insG		intron_variant		ENST00000628067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANO1	ENST00000678030.1	c.463dup	p.Leu155ProfsTer170	frameshift_variant	1/1			P1
SLC25A22	ENST00000628067.3	c.-164+135_-164+136insG		intron_variant		1	NM_001191061.2	P1

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 344 AN: 148432 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000201

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000224

Gnomad OTH AF: 0.00148

GnomAD4 exome AF: 0.000460 AC: 113 AN: 245682 Hom.: 0 Cov.: 0 AF XY: 0.000361 AC XY: 45 AN XY: 124542

Gnomad4 AFR exome AF: 0.00698

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000219

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000144

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.000980

GnomAD4 genome AF: 0.00233 AC: 346 AN: 148530 Hom.: 4 Cov.: 33 AF XY: 0.00239 AC XY: 173 AN XY: 72428

Gnomad4 AFR AF: 0.00767

Gnomad4 AMR AF: 0.00113

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000201

Gnomad4 NFE AF: 0.000224

Gnomad4 OTH AF: 0.00146

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1312807369; hg19: chr11-798081;