6-138092856-A-T

Variant names:

• chr6-138092856-A-T
• rs651662
• NM_022121.5:c.356-588T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022121.5(PERP):​c.356-588T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: PERP NM_022121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 5 publications found

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]

PERP Gene-Disease associations (from GenCC):

• Olmsted syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• erythrokeratodermia variabilis et progressiva 7

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mutilating palmoplantar keratoderma with periorificial keratotic plaques

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022121.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PERP	NM_022121.5	MANE Select	c.356-588T>A		intron	N/A	NP_071404.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PERP	ENST00000421351.4	TSL:1 MANE Select	c.356-588T>A		intron	N/A	ENSP00000397157.2	Q96FX8

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.61
PhyloP100		-0.10
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

Other links and lift over

dbSNP: rs651662; hg19: chr6-138413993;