Genetic Variant GDPD1:p.Arg204Gly (chr17-59267074-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182569.4(GDPD1):c.610C>G(p.Arg204Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,612,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GDPD1
NM_182569.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

GDPD1 (HGNC:20883): (glycerophosphodiester phosphodiesterase domain containing 1) This gene encodes a member of the glycerophosphodiester phosphodiesterase family of enzymes that catalyze the hydrolysis of deacylated glycerophospholipids to glycerol phosphate and alcohol. The encoded protein is localized to the cytoplasm and concentrates near the perinuclear region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

GDPD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD1	NM_182569.4 link	c.610C>G	p.Arg204Gly	missense_variant	Exon 7 of 10	ENST00000284116.9	NP_872375.2	Q8N9F7-1
GDPD1	NM_001165994.2 link	c.610C>G	p.Arg204Gly	missense_variant	Exon 7 of 9		NP_001159466.1	Q8N9F7-2
GDPD1	NM_001165993.2 link	c.610C>G	p.Arg204Gly	missense_variant	Exon 7 of 10		NP_001159465.1	Q8N9F7-3
GDPD1	XM_017024521.2 link	c.331C>G	p.Arg111Gly	missense_variant	Exon 4 of 7		XP_016880010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPD1	ENST00000284116.9 link	c.610C>G	p.Arg204Gly	missense_variant	Exon 7 of 10	1	NM_182569.4	ENSP00000284116.4		Q8N9F7-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251372

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1460372

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726590

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:

0.00000990

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

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

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.610C>G (p.R204G) alteration is located in exon 7 (coding exon 7) of the GDPD1 gene. This alteration results from a C to G substitution at nucleotide position 610, causing the arginine (R) at amino acid position 204 to be replaced by a glycine (G). 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

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;.;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.2

D;.;.

REVEL

Benign

0.23

Sift

Benign

0.048

D;.;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.54

P;.;P

Vest4

0.82

MutPred

0.62

Gain of catalytic residue at V205 (P = 0.0143);Gain of catalytic residue at V205 (P = 0.0143);Gain of catalytic residue at V205 (P = 0.0143);

MVP

0.36

MPC

0.75

ClinPred

0.97

GERP RS

4.6

Varity_R

0.64

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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