Genetic Variant GDPD4:p.Val484Phe (chr11-77229172-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182833.3(GDPD4):c.1450G>T(p.Val484Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,600,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

GDPD4
NM_182833.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.50

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]

GDPD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04594308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3 link	c.1450G>T	p.Val484Phe	missense_variant	Exon 15 of 17	ENST00000315938.5	NP_878253.1	Q6W3E5-2
GDPD4	XM_011544834.1 link	c.1528G>T	p.Val510Phe	missense_variant	Exon 15 of 18		XP_011543136.1
GDPD4	XM_047426557.1 link	c.856G>T	p.Val286Phe	missense_variant	Exon 11 of 13		XP_047282513.1
GDPD4	XM_047426558.1 link	c.856G>T	p.Val286Phe	missense_variant	Exon 11 of 13		XP_047282514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPD4	ENST00000315938.5 link	c.1450G>T	p.Val484Phe	missense_variant	Exon 15 of 17	1	NM_182833.3	ENSP00000320815.4		Q6W3E5-2
GDPD4	ENST00000376217.6 link	c.1450G>T	p.Val484Phe	missense_variant	Exon 14 of 17	1		ENSP00000365390.2		Q6W3E5-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151978

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

246690

Hom.:

AF XY:

0.0000451

AC XY:

AN XY:

133162

show subpopulations

Gnomad AFR exome

AF:

0.0000623

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:

0.0000537

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1448878

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

720860

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000181

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1450G>T (p.V484F) alteration is located in exon 14 (coding exon 13) of the GDPD4 gene. This alteration results from a G to T substitution at nucleotide position 1450, causing the valine (V) at amino acid position 484 to be replaced by a phenylalanine (F). 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

0.079

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0020

DANN

Benign

0.77

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.091

Sift

Benign

0.043

D;T

Sift4G

Benign

0.083

T;T

Polyphen

0.0010

.;B

Vest4

0.24

MutPred

0.38

Loss of catalytic residue at V484 (P = 0.0132);Loss of catalytic residue at V484 (P = 0.0132);

MVP

0.040

MPC

0.062

ClinPred

0.086

GERP RS

-10

Varity_R

0.063

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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