11-797834-C-A

Position:

• chr11-797834-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000678030.1(PANO1):​c.209C>A​(p.Ala70Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 398,670 control chromosomes in the GnomAD database, including 632 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (176 hom., cov: 33)
  • Exomes 𝑓: 0.055 (456 hom.)
• Consequence: PANO1 ENST00000678030.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.77

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030249357).
• BP6: Variant 11-797834-C-A is Benign according to our data. Variant chr11-797834-C-A is described in ClinVar as [Benign]. Clinvar id is 1182814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A22	NM_001191061.2	c.-164+383G>T		intron_variant		ENST00000628067.3	NP_001177990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANO1	ENST00000678030.1	c.209C>A	p.Ala70Asp	missense_variant	1/1			ENSP00000503591.1
SLC25A22	ENST00000628067.3	c.-164+383G>T		intron_variant		1	NM_001191061.2	ENSP00000486058.1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6539 AN: 152204 Hom.: 176 Cov.: 33

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0511

GnomAD4 exome AF: 0.0546 AC: 13458 AN: 246348 Hom.: 456 Cov.: 0 AF XY: 0.0560 AC XY: 6988 AN XY: 124868

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0323

Gnomad4 ASJ exome AF: 0.0550

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00922

Gnomad4 FIN exome AF: 0.0526

Gnomad4 NFE exome AF: 0.0672

Gnomad4 OTH exome AF: 0.0514

GnomAD4 genome AF: 0.0429 AC: 6535 AN: 152322 Hom.: 176 Cov.: 33 AF XY: 0.0410 AC XY: 3055 AN XY: 74488

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0537 Hom.: 27

Bravo AF: 0.0407

TwinsUK AF: 0.0677 AC: 251

ALSPAC AF: 0.0685 AC: 264

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.76
DEOGEN2	Benign	0.088	T
FATHMM_MKL	Benign	0.014	N
MetaRNN	Benign	0.0030	T
Sift4G	Benign	0.23	T
Vest4		0.086
MVP		0.42
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.099
gMVP		0.036

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

Publications

LitVar

Other links and lift over

dbSNP: rs112750986; hg19: chr11-797834;