11-77227914-C-T

Variant summary

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

The NM_182833.3(GDPD4):​c.1475G>A​(p.Arg492Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,610,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

GDPD4
NM_182833.3 missense, splice_region

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0560
Variant links:
Genes affected
GDPD4 (HGNC:24849): (glycerophosphodiester phosphodiesterase domain containing 4) Predicted to enable metal ion binding activity and phosphoric diester hydrolase activity. Predicted to be involved in lipid metabolic process. Predicted to be integral component of membrane. [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 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
GDPD4NM_182833.3 linkc.1475G>A p.Arg492Gln missense_variant, splice_region_variant Exon 16 of 17 ENST00000315938.5 NP_878253.1 Q6W3E5-2
GDPD4XM_011544834.1 linkc.1553G>A p.Arg518Gln missense_variant, splice_region_variant Exon 16 of 18 XP_011543136.1
GDPD4XM_047426557.1 linkc.881G>A p.Arg294Gln missense_variant, splice_region_variant Exon 12 of 13 XP_047282513.1
GDPD4XM_047426558.1 linkc.881G>A p.Arg294Gln missense_variant, splice_region_variant Exon 12 of 13 XP_047282514.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GDPD4ENST00000315938.5 linkc.1475G>A p.Arg492Gln missense_variant, splice_region_variant Exon 16 of 17 1 NM_182833.3 ENSP00000320815.4 Q6W3E5-2
GDPD4ENST00000376217.6 linkc.1475G>A p.Arg492Gln missense_variant, splice_region_variant Exon 15 of 17 1 ENSP00000365390.2 Q6W3E5-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152180
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251326
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135840
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:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1458768
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
725918
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
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:
0.0000171
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152180
Hom.:
0
Cov.:
31
AF XY:
0.0000403
AC XY:
3
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000381
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1475G>A (p.R492Q) alteration is located in exon 15 (coding exon 14) of the GDPD4 gene. This alteration results from a G to A substitution at nucleotide position 1475, causing the arginine (R) at amino acid position 492 to be replaced by a glutamine (Q). 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
0.087
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
13
DANN
Benign
0.92
DEOGEN2
Benign
0.0012
T;.
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.050
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.058
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.68
N;N
REVEL
Benign
0.048
Sift
Benign
0.36
T;T
Sift4G
Benign
0.54
T;T
Polyphen
0.32
.;B
Vest4
0.19
MVP
0.14
MPC
0.055
ClinPred
0.035
T
GERP RS
0.91
Varity_R
0.028
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.27
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.27
Position offset: 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: rs771147328; hg19: chr11-76938959; COSMIC: COSV60020764; COSMIC: COSV60020764; API