Variant 20-5575950-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019593.5(GPCPD1):c.734G>A(p.Gly245Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000229 in 1,600,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

GPCPD1
NM_019593.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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]

GPCPD1 links:

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=0.11423054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPCPD1	NM_019593.5 linkuse as main transcript	c.734G>A	p.Gly245Asp	missense_variant	9/20	ENST00000379019.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPCPD1	ENST00000379019.7 linkuse as main transcript	c.734G>A	p.Gly245Asp	missense_variant	9/20	1	NM_019593.5	P1
GPCPD1	ENST00000481038.5 linkuse as main transcript	n.2142G>A		non_coding_transcript_exon_variant	4/15	2
GPCPD1	ENST00000481690.2 linkuse as main transcript	c.*352G>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	3

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.000353

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000138

AC:

AN:

247130

Hom.:

AF XY:

0.0000972

AC XY:

AN XY:

133782

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000235

AC:

341

AN:

1448074

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

179

AN XY:

720794

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.0000466

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000171

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.000353

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000132

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.734G>A (p.G245D) alteration is located in exon 9 (coding exon 8) of the GPCPD1 gene. This alteration results from a G to A substitution at nucleotide position 734, causing the glycine (G) at amino acid position 245 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

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.12

Eigen_PC

Benign

0.084

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0074

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.93

REVEL

Benign

0.065

Sift

Benign

0.24

Sift4G

Benign

0.52

Polyphen

0.13

Vest4

0.24

MVP

0.30

MPC

0.71

ClinPred

0.051

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over