Genetic Variant GDPD1:p.Leu104Ile (chr17-59245538-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_182569.4(GDPD1):c.310C>A(p.Leu104Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000871 in 1,607,206 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GDPD1
NM_182569.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28914237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD1	NM_182569.4 link	c.310C>A	p.Leu104Ile	missense_variant	Exon 3 of 10	ENST00000284116.9	NP_872375.2	Q8N9F7-1
GDPD1	NM_001165994.2 link	c.310C>A	p.Leu104Ile	missense_variant	Exon 3 of 9		NP_001159466.1	Q8N9F7-2
GDPD1	NM_001165993.2 link	c.310C>A	p.Leu104Ile	missense_variant	Exon 3 of 10		NP_001159465.1	Q8N9F7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPD1	ENST00000284116.9 link	c.310C>A	p.Leu104Ile	missense_variant	Exon 3 of 10	1	NM_182569.4	ENSP00000284116.4		Q8N9F7-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152166

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248164

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

134090

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

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:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1455040

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

723880

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

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:

0.00000632

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310C>A (p.L104I) alteration is located in exon 3 (coding exon 3) of the GDPD1 gene. This alteration results from a C to A substitution at nucleotide position 310, causing the leucine (L) at amino acid position 104 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

0.095

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.052

T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.11

Sift

Benign

0.099

T;.;.

Sift4G

Benign

0.22

T;T;T

Polyphen

0.91

P;.;P

Vest4

0.32

MutPred

0.66

Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);

MVP

0.47

MPC

0.60

ClinPred

0.42

GERP RS

4.4

Varity_R

0.18

gMVP

0.35

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.

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