20-5558033-C-T

Variant summary

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

The NM_019593.5(GPCPD1):​c.1741G>A​(p.Val581Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,597,202 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 (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

GPCPD1
NM_019593.5 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87
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
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19164282).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPCPD1NM_019593.5 linkc.1741G>A p.Val581Ile missense_variant Exon 19 of 20 ENST00000379019.7 NP_062539.1 Q9NPB8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPCPD1ENST00000379019.7 linkc.1741G>A p.Val581Ile missense_variant Exon 19 of 20 1 NM_019593.5 ENSP00000368305.4 Q9NPB8
GPCPD1ENST00000418646.5 linkc.514G>A p.Val172Ile missense_variant Exon 6 of 7 5 ENSP00000396720.1 H0Y565
GPCPD1ENST00000481038.5 linkn.3149G>A non_coding_transcript_exon_variant Exon 14 of 15 2

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000845
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:
0.000478
GnomAD3 exomes
AF:
0.0000677
AC:
17
AN:
251068
Hom.:
0
AF XY:
0.0000811
AC XY:
11
AN XY:
135708
show subpopulations
Gnomad AFR exome
AF:
0.000800
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:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000436
AC:
63
AN:
1444956
Hom.:
1
Cov.:
25
AF XY:
0.0000347
AC XY:
25
AN XY:
719994
show subpopulations
Gnomad4 AFR exome
AF:
0.000754
Gnomad4 AMR exome
AF:
0.0000672
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:
0.0000292
Gnomad4 OTH exome
AF:
0.0000502
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.000842
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:
0.000473
Alfa
AF:
0.000178
Hom.:
0
Bravo
AF:
0.000317
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1741G>A (p.V581I) alteration is located in exon 19 (coding exon 18) of the GPCPD1 gene. This alteration results from a G to A substitution at nucleotide position 1741, causing the valine (V) at amino acid position 581 to be replaced by an isoleucine (I). 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
0.097
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.020
N
REVEL
Benign
0.23
Sift
Benign
0.52
T
Sift4G
Benign
0.68
T
Polyphen
1.0
D
Vest4
0.56
MVP
0.41
MPC
1.1
ClinPred
0.12
T
GERP RS
5.7
Varity_R
0.076
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: rs532239169; hg19: chr20-5538679; COSMIC: COSV66832115; COSMIC: COSV66832115; API