chr6-138107131-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022121.5(PERP):ā€‹c.210G>Cā€‹(p.Glu70Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000412 in 1,603,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000043 ( 0 hom. )

Consequence

PERP
NM_022121.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -11.2
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0539805).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PERPNM_022121.5 linkuse as main transcriptc.210G>C p.Glu70Asp missense_variant 1/3 ENST00000421351.4 NP_071404.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PERPENST00000421351.4 linkuse as main transcriptc.210G>C p.Glu70Asp missense_variant 1/31 NM_022121.5 ENSP00000397157 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000852
AC:
2
AN:
234872
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
129196
show subpopulations
Gnomad AFR exome
AF:
0.0000695
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000952
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000434
AC:
63
AN:
1451686
Hom.:
0
Cov.:
32
AF XY:
0.0000360
AC XY:
26
AN XY:
721764
show subpopulations
Gnomad4 AFR exome
AF:
0.0000302
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000560
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000848
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.00000828
AC:
1
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 17, 2023The c.210G>C (p.E70D) alteration is located in exon 1 (coding exon 1) of the PERP gene. This alteration results from a G to C substitution at nucleotide position 210, causing the glutamic acid (E) at amino acid position 70 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
0.0010
DANN
Benign
0.74
DEOGEN2
Benign
0.36
T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.3
FATHMM_MKL
Benign
0.0067
N
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.054
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.47
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.10
N
REVEL
Benign
0.26
Sift
Benign
0.76
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.053
MutPred
0.33
Loss of helix (P = 0.0795);
MVP
0.27
MPC
0.47
ClinPred
0.053
T
GERP RS
-9.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.053
gMVP
0.51

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376957775; hg19: chr6-138428268; API