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GeneBe

20-5547795-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019593.5(GPCPD1):c.1885C>T(p.Arg629Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,609,462 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R629H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

GPCPD1
NM_019593.5 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83
Variant links:
Genes affected
GPCPD1 (HGNC:26957): (glycerophosphocholine phosphodiesterase 1) Predicted to enable glycerophosphocholine phosphodiesterase activity. Predicted to be involved in glycerophospholipid catabolic process. Predicted to act upstream of or within skeletal muscle tissue development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.19212249).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPCPD1NM_019593.5 linkuse as main transcriptc.1885C>T p.Arg629Cys missense_variant 20/20 ENST00000379019.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPCPD1ENST00000379019.7 linkuse as main transcriptc.1885C>T p.Arg629Cys missense_variant 20/201 NM_019593.5 P1
GPCPD1ENST00000418646.5 linkuse as main transcriptc.661C>T p.Arg221Cys missense_variant 7/75
GPCPD1ENST00000462080.1 linkuse as main transcriptn.179C>T non_coding_transcript_exon_variant 2/22
GPCPD1ENST00000481038.5 linkuse as main transcriptn.3293C>T non_coding_transcript_exon_variant 15/152

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000263
AC:
4
AN:
152218
Hom.:
1
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:
0.000384
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
250148
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135250
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000585
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000165
AC:
24
AN:
1457126
Hom.:
0
Cov.:
28
AF XY:
0.0000207
AC XY:
15
AN XY:
725168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000672
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000931
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000993
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000263
AC:
4
AN:
152336
Hom.:
1
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756
ExAC
?
    Exome Aggregation Consortium database
AF:
0.0000165
AC:
2

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 GeneticsNov 08, 2022The c.1885C>T (p.R629C) alteration is located in exon 20 (coding exon 19) of the GPCPD1 gene. This alteration results from a C to T substitution at nucleotide position 1885, causing the arginine (R) at amino acid position 629 to be replaced by a cysteine (C). 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
0.18
BayesDel_addAF
Benign
-0.029
T
BayesDel_noAF
Benign
-0.10
Cadd
Pathogenic
31
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.049
T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.22
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.043
D
Polyphen
1.0
D
Vest4
0.38
MVP
0.37
MPC
1.3
ClinPred
0.85
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
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: rs185880154; hg19: chr20-5528441; COSMIC: COSV66832168; COSMIC: COSV66832168; API