chr11-77243806-C-A

Variant names:

• chr11-77243806-C-A
• rs1451048684
• NM_182833.3:c.1129G>T

Variant summary

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

The NM_182833.3(GDPD4):​c.1129G>T​(p.Val377Leu) 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 1,461,530 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GDPD4 NM_182833.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.207

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=0.046863526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3	c.1129G>T	p.Val377Leu	missense_variant	Exon 13 of 17	ENST00000315938.5	NP_878253.1
GDPD4	XM_011544834.1	c.1207G>T	p.Val403Leu	missense_variant	Exon 13 of 18		XP_011543136.1
GDPD4	XM_047426557.1	c.795+1475G>T		intron_variant	Intron 10 of 12		XP_047282513.1
GDPD4	XM_047426558.1	c.795+1475G>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	c.1129G>T	p.Val377Leu	missense_variant	Exon 13 of 17	1	NM_182833.3	ENSP00000320815.4
GDPD4	ENST00000376217.6	c.1129G>T	p.Val377Leu	missense_variant	Exon 12 of 17	1		ENSP00000365390.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461530 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727106

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1129G>T (p.V377L) alteration is located in exon 12 (coding exon 11) of the GDPD4 gene. This alteration results from a G to T substitution at nucleotide position 1129, causing the valine (V) at amino acid position 377 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.060
DANN	Benign	0.70
DEOGEN2	Benign	0.0012	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.090	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N;N
REVEL	Benign	0.017
Sift	Benign	0.54	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0030	.;B
Vest4		0.055
MutPred		0.52		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.048
MPC		0.050
ClinPred		0.042	T
GERP RS		-4.6
Varity_R		0.027
gMVP		0.38

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

Other links and lift over

dbSNP: rs1451048684; hg19: chr11-76954851;