chr11-77243815-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_182833.3(GDPD4):​c.1120G>T​(p.Val374Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V374I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GDPD4
NM_182833.3 missense

Scores

3
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GDPD4NM_182833.3 linkc.1120G>T p.Val374Phe missense_variant Exon 13 of 17 ENST00000315938.5 NP_878253.1 Q6W3E5-2
GDPD4XM_011544834.1 linkc.1198G>T p.Val400Phe missense_variant Exon 13 of 18 XP_011543136.1
GDPD4XM_047426557.1 linkc.795+1466G>T intron_variant Intron 10 of 12 XP_047282513.1
GDPD4XM_047426558.1 linkc.795+1466G>T intron_variant Intron 10 of 12 XP_047282514.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GDPD4ENST00000315938.5 linkc.1120G>T p.Val374Phe missense_variant Exon 13 of 17 1 NM_182833.3 ENSP00000320815.4 Q6W3E5-2
GDPD4ENST00000376217.6 linkc.1120G>T p.Val374Phe missense_variant Exon 12 of 17 1 ENSP00000365390.2 Q6W3E5-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461458
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727048
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.
Eigen
Uncertain
0.21
Eigen_PC
Benign
0.040
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.78
T;T
M_CAP
Benign
0.013
T
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
.;D
Vest4
0.81
MutPred
0.62
Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
0.35
MPC
0.37
ClinPred
1.0
D
GERP RS
3.4
Varity_R
0.72
gMVP
0.91

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: rs779270640; hg19: chr11-76954860; API