chrX-70429557-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017711.4(GDPD2):​c.1001C>T​(p.Thr334Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,206,906 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.00010 ( 0 hom. 32 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.279
Variant links:
Genes affected
GDPD2 (HGNC:25974): (glycerophosphodiester phosphodiesterase domain containing 2) This gene encodes a member of the glycerophosphodiester phosphodiesterase enzyme family. The encoded protein hydrolyzes glycerophosphoinositol to produce inositol 1-phosphate and glycerol. This protein may have a role in osteoblast differentiation and growth. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013724923).
BS2
High Hemizygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GDPD2NM_017711.4 linkc.1001C>T p.Thr334Met missense_variant Exon 11 of 16 ENST00000374382.4 NP_060181.2 Q9HCC8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GDPD2ENST00000374382.4 linkc.1001C>T p.Thr334Met missense_variant Exon 11 of 16 1 NM_017711.4 ENSP00000363503.3 Q9HCC8-1

Frequencies

GnomAD3 genomes
AF:
0.000107
AC:
12
AN:
111801
Hom.:
0
Cov.:
22
AF XY:
0.0000294
AC XY:
1
AN XY:
33971
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000944
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000380
Gnomad FIN
AF:
0.00115
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000565
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000186
AC:
34
AN:
183091
Hom.:
0
AF XY:
0.000192
AC XY:
13
AN XY:
67575
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000144
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00100
Gnomad NFE exome
AF:
0.000184
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000995
AC:
109
AN:
1095051
Hom.:
0
Cov.:
30
AF XY:
0.0000888
AC XY:
32
AN XY:
360523
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000142
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000166
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00113
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.000283
GnomAD4 genome
AF:
0.000107
AC:
12
AN:
111855
Hom.:
0
Cov.:
22
AF XY:
0.0000294
AC XY:
1
AN XY:
34035
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000943
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000381
Gnomad4 FIN
AF:
0.00115
Gnomad4 NFE
AF:
0.0000565
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000670
Hom.:
2
Bravo
AF:
0.0000416
ExAC
AF:
0.000305
AC:
37
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1001C>T (p.T334M) alteration is located in exon 11 (coding exon 10) of the GDPD2 gene. This alteration results from a C to T substitution at nucleotide position 1001, causing the threonine (T) at amino acid position 334 to be replaced by a methionine (M). 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
0.077
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.98
CADD
Benign
6.0
DANN
Benign
0.97
DEOGEN2
Benign
0.046
.;.;.;T
FATHMM_MKL
Benign
0.058
N
LIST_S2
Benign
0.60
T;.;T;T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.014
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;.;L
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Benign
0.024
Sift
Benign
0.065
T;T;T;T
Sift4G
Uncertain
0.054
T;T;T;T
Polyphen
0.086
.;.;.;B
Vest4
0.093
MVP
0.36
MPC
0.53
ClinPred
0.038
T
GERP RS
0.38
Varity_R
0.052
gMVP
0.63

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: rs200782055; hg19: chrX-69649407; COSMIC: COSV65533749; API