4-20713534-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001258345.3(PACRGL):ā€‹c.604A>Cā€‹(p.Thr202Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,606,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

PACRGL
NM_001258345.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99
Variant links:
Genes affected
PACRGL (HGNC:28442): (parkin coregulated like)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26453316).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PACRGLNM_001258345.3 linkuse as main transcriptc.604A>C p.Thr202Pro missense_variant 7/9 ENST00000503585.6 NP_001245274.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PACRGLENST00000503585.6 linkuse as main transcriptc.604A>C p.Thr202Pro missense_variant 7/92 NM_001258345.3 ENSP00000423881 P1Q8N7B6-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1454246
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
723940
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 12, 2021The c.604A>C (p.T202P) alteration is located in exon 7 (coding exon 6) of the PACRGL gene. This alteration results from a A to C substitution at nucleotide position 604, causing the threonine (T) at amino acid position 202 to be replaced by a proline (P). 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
0.10
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.014
T;.;.;.;.;.;.;.;T;T
Eigen
Benign
-0.0084
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.84
T;.;.;T;T;T;T;.;T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.26
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
-0.14
N;N;N;.;.;.;.;N;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.51
N;N;N;D;N;N;D;N;N;N
REVEL
Benign
0.21
Sift
Benign
0.24
T;T;T;D;D;D;D;T;T;T
Sift4G
Benign
0.37
T;T;T;D;T;D;D;T;D;D
Polyphen
0.010
B;B;B;.;.;.;.;B;D;.
Vest4
0.66
MutPred
0.47
Gain of disorder (P = 0.0526);Gain of disorder (P = 0.0526);Gain of disorder (P = 0.0526);.;.;Gain of disorder (P = 0.0526);.;Gain of disorder (P = 0.0526);.;.;
MVP
0.25
MPC
0.089
ClinPred
0.95
D
GERP RS
5.6
Varity_R
0.28
gMVP
0.60

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: rs1738318545; hg19: chr4-20715157; API