11-77243806-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182833.3(GDPD4):​c.1129G>C​(p.Val377Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GDPD4 NM_182833.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046908796).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182833.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDPD4	NM_182833.3	MANE Select	c.1129G>C	p.Val377Leu	missense	Exon 13 of 17	NP_878253.1	Q6W3E5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDPD4	ENST00000315938.5	TSL:1 MANE Select	c.1129G>C	p.Val377Leu	missense	Exon 13 of 17	ENSP00000320815.4	Q6W3E5-2
	GDPD4	ENST00000376217.6	TSL:1	c.1129G>C	p.Val377Leu	missense	Exon 12 of 17	ENSP00000365390.2	Q6W3E5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.056
DANN	Benign	0.58
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.090	N
PhyloP100		0.21
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.017
Sift	Benign	0.54	T
Sift4G	Benign	0.40	T
Polyphen		0.0030	B
Vest4		0.055
MutPred		0.52		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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1451048684; hg19: chr11-76954851;