11-77229172-C-T

Variant names:

• chr11-77229172-C-T
• rs548426468
• NM_182833.3:c.1450G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182833.3(GDPD4):​c.1450G>A​(p.Val484Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000966 in 1,448,880 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. V484F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: GDPD4 NM_182833.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50

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]

ACMG classification

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=0.037119925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3	c.1450G>A	p.Val484Ile	missense_variant	Exon 15 of 17	ENST00000315938.5	NP_878253.1
GDPD4	XM_011544834.1	c.1528G>A	p.Val510Ile	missense_variant	Exon 15 of 18		XP_011543136.1
GDPD4	XM_047426557.1	c.856G>A	p.Val286Ile	missense_variant	Exon 11 of 13		XP_047282513.1
GDPD4	XM_047426558.1	c.856G>A	p.Val286Ile	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	c.1450G>A	p.Val484Ile	missense_variant	Exon 15 of 17	1	NM_182833.3	ENSP00000320815.4
GDPD4	ENST00000376217.6	c.1450G>A	p.Val484Ile	missense_variant	Exon 14 of 17	1		ENSP00000365390.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000122 AC: 3 AN: 246690 Hom.: 0 AF XY: 0.00000751 AC XY: 1 AN XY: 133162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000966 AC: 14 AN: 1448880 Hom.: 0 Cov.: 27 AF XY: 0.0000125 AC XY: 9 AN XY: 720860

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000453

Gnomad4 OTH exome AF: 0.0000669

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0020
DANN	Benign	0.55
DEOGEN2	Benign	0.0012	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.020
Sift	Benign	0.47	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.0010	.;B
Vest4		0.075
MutPred		0.37		Loss of catalytic residue at V484 (P = 0.0983);Loss of catalytic residue at V484 (P = 0.0983);
MVP		0.12
MPC		0.044
ClinPred		0.033	T
GERP RS		-10
Varity_R		0.022
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs548426468; hg19: chr11-76940217;