rs2484066

Positions:

• chr6-138095981-T-G

Variant summary

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

The NM_022121.5(PERP):​c.355+373A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,984 control chromosomes in the GnomAD database, including 20,024 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 0.50 (20024 hom., cov: 31)
• Consequence: PERP NM_022121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PERP	NM_022121.5	c.355+373A>C		intron_variant		ENST00000421351.4	NP_071404.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PERP	ENST00000421351.4	c.355+373A>C		intron_variant		1	NM_022121.5	ENSP00000397157	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76202 AN: 151866 Hom.: 20018 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.502 AC: 76227 AN: 151984 Hom.: 20024 Cov.: 31 AF XY: 0.491 AC XY: 36499 AN XY: 74312

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.488

Alfa AF: 0.533 Hom.: 23770

Bravo AF: 0.491

Asia WGS AF: 0.233 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.77

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: rs2484066; hg19: chr6-138417118; COSMIC: COSV69827758;