11-77243797-C-A

Variant names:

• chr11-77243797-C-A
• NM_182833.3:c.1138G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182833.3(GDPD4):​c.1138G>T​(p.Gly380Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GDPD4 NM_182833.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3	c.1138G>T	p.Gly380Cys	missense_variant	Exon 13 of 17	ENST00000315938.5	NP_878253.1
GDPD4	XM_011544834.1	c.1216G>T	p.Gly406Cys	missense_variant	Exon 13 of 18		XP_011543136.1
GDPD4	XM_047426557.1	c.795+1484G>T		intron_variant	Intron 10 of 12		XP_047282513.1
GDPD4	XM_047426558.1	c.795+1484G>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.1138G>T	p.Gly380Cys	missense_variant	Exon 13 of 17	1	NM_182833.3	ENSP00000320815.4
GDPD4	ENST00000376217.6	c.1138G>T	p.Gly380Cys	missense_variant	Exon 12 of 17	1		ENSP00000365390.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1138G>T (p.G380C) 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 1138, causing the glycine (G) at amino acid position 380 to be replaced by a cysteine (C). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-7.5	D;D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	.;D
Vest4		0.54
MutPred		0.65		Loss of disorder (P = 0.0855);Loss of disorder (P = 0.0855);
MVP		0.51
MPC		0.34
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.84
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-76954842;