17-59245538-C-A

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

5
14

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]

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
GDPD1NM_182569.4 linkc.310C>A p.Leu104Ile missense_variant Exon 3 of 10 ENST00000284116.9 NP_872375.2 Q8N9F7-1
GDPD1NM_001165994.2 linkc.310C>A p.Leu104Ile missense_variant Exon 3 of 9 NP_001159466.1 Q8N9F7-2
GDPD1NM_001165993.2 linkc.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
GDPD1ENST00000284116.9 linkc.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:
5
AN:
152166
Hom.:
0
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:
0.00
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:
4
AN:
248164
Hom.:
0
AF XY:
0.0000298
AC XY:
4
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:
9
AN:
1455040
Hom.:
0
Cov.:
27
AF XY:
0.00000967
AC XY:
7
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:
5
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
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:
2

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
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Benign
0.92
DEOGEN2
Benign
0.052
T;.;.
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.6
M;M;M
PrimateAI
Uncertain
0.53
T
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
T
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.

Other links and lift over

dbSNP: rs765102238; hg19: chr17-57322899; API