rs651662

chr6-138092856-A-Gchr6-138092856-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022121.5(PERP):c.356-588T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,862 control chromosomes in the GnomAD database, including 22,358 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.

• Frequency: Genomes: 𝑓 0.54 (22358 hom., cov: 30)
• Consequence: PERP NM_022121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

Genes affected

PERP (HGNC:17637): (p53 apoptosis effector related to PMP22) Involved in activation of cysteine-type endopeptidase activity. Predicted to be located in plasma membrane. Predicted to be active in cell-cell junction. Implicated in erythrokeratodermia variabilis and mutilating palmoplantar keratoderma with periorificial keratotic plaques. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PERP	NM_022121.5	c.356-588T>C		intron_variant		ENST00000421351.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PERP	ENST00000421351.4	c.356-588T>C		intron_variant		1	NM_022121.5	P1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81494 AN: 151746 Hom.: 22340 Cov.: 30

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81548 AN: 151862 Hom.: 22358 Cov.: 30 AF XY: 0.544 AC XY: 40340 AN XY: 74208

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.574

Alfa AF: 0.554 Hom.: 10275

Bravo AF: 0.533

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	4.2
Dann	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs651662; hg19: chr6-138413993;