6-138104895-C-T

Position:

• chr6-138104895-C-T

Variant summary

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

The ENST00000421351.4(PERP):​c.214+2232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 151,948 control chromosomes in the GnomAD database, including 54,639 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 0.85 (54639 hom., cov: 33)
• Consequence: PERP ENST00000421351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PERP	NM_022121.5	c.214+2232G>A		intron_variant		ENST00000421351.4	NP_071404.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PERP	ENST00000421351.4	c.214+2232G>A		intron_variant		1	NM_022121.5	ENSP00000397157	P1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128757 AN: 151828 Hom.: 54598 Cov.: 33

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.848 AC: 128856 AN: 151948 Hom.: 54639 Cov.: 33 AF XY: 0.843 AC XY: 62586 AN XY: 74280

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.845

Alfa AF: 0.857 Hom.: 28839

Bravo AF: 0.849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.67

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: rs1556640; hg19: chr6-138426032; COSMIC: COSV69827763;