Genetic Variant GDPD4:p.Val374Ile (chr11-77243815-C-T) – 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.1120G>A(p.Val374Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

GDPD4
NM_182833.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

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=0.051178455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3 link	c.1120G>A	p.Val374Ile	missense_variant	Exon 13 of 17	ENST00000315938.5	NP_878253.1	Q6W3E5-2
GDPD4	XM_011544834.1 link	c.1198G>A	p.Val400Ile	missense_variant	Exon 13 of 18		XP_011543136.1
GDPD4	XM_047426557.1 link	c.795+1466G>A		intron_variant	Intron 10 of 12		XP_047282513.1
GDPD4	XM_047426558.1 link	c.795+1466G>A		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.1120G>A	p.Val374Ile	missense_variant	Exon 13 of 17	1	NM_182833.3	ENSP00000320815.4		Q6W3E5-2
GDPD4	ENST00000376217.6 link	c.1120G>A	p.Val374Ile	missense_variant	Exon 12 of 17	1		ENSP00000365390.2		Q6W3E5-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251212

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461458

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1120G>A (p.V374I) alteration is located in exon 12 (coding exon 11) of the GDPD4 gene. This alteration results from a G to A substitution at nucleotide position 1120, causing the valine (V) at amino acid position 374 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.092

Sift

Benign

0.045

D;T

Sift4G

Benign

0.12

T;T

Polyphen

0.94

.;P

Vest4

0.18

MutPred

0.46

Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.21

MPC

0.15

ClinPred

0.13

GERP RS

3.4

Varity_R

0.099

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.

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