dbSNP rs1034560793: GDPD4:p.Val425Leu (chr11-77233141-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.1273G>T(p.Val425Leu) 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 1,461,644 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. 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. V425I) 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.86

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=0.02474311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3 link	c.1273G>T	p.Val425Leu	missense_variant	Exon 14 of 17	ENST00000315938.5	NP_878253.1	Q6W3E5-2
GDPD4	XM_011544834.1 link	c.1351G>T	p.Val451Leu	missense_variant	Exon 14 of 18		XP_011543136.1
GDPD4	XM_047426557.1 link	c.796-3909G>T		intron_variant	Intron 10 of 12		XP_047282513.1
GDPD4	XM_047426558.1 link	c.796-3909G>T		intron_variant	Intron 10 of 12		XP_047282514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPD4	ENST00000315938.5 link	c.1273G>T	p.Val425Leu	missense_variant	Exon 14 of 17	1	NM_182833.3	ENSP00000320815.4		Q6W3E5-2
GDPD4	ENST00000376217.6 link	c.1273G>T	p.Val425Leu	missense_variant	Exon 13 of 17	1		ENSP00000365390.2		Q6W3E5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251364

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461644

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0010

DANN

Benign

0.21

DEOGEN2

Benign

0.0060

T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.2

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.054

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.079

MutPred

0.60

Loss of stability (P = 0.2595);Loss of stability (P = 0.2595);

MVP

0.061

MPC

0.049

ClinPred

0.047

GERP RS

-9.8

Varity_R

0.029

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over