16-19510910-T-C

Position:

• chr16-19510910-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000353258.8(GDE1):​c.472A>G​(p.Arg158Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GDE1 ENST00000353258.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

Genes affected

GDE1 (HGNC:29644): (glycerophosphodiester phosphodiesterase 1) Predicted to enable glycerophosphodiester phosphodiesterase activity; glycerophosphoinositol glycerophosphodiesterase activity; and lysophospholipase activity. Predicted to be involved in N-acylethanolamine metabolic process; ethanolamine metabolic process; and phospholipid metabolic process. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21537414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDE1	NM_016641.4	c.472A>G	p.Arg158Gly	missense_variant	3/6	ENST00000353258.8	NP_057725.1
GDE1	NM_001324067.2	c.472A>G	p.Arg158Gly	missense_variant	3/5		NP_001310996.1
GDE1	NM_001324066.2	c.142A>G	p.Arg48Gly	missense_variant	3/6		NP_001310995.1
GDE1	NR_136689.2	n.606A>G		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDE1	ENST00000353258.8	c.472A>G	p.Arg158Gly	missense_variant	3/6	1	NM_016641.4	ENSP00000261386	P1
GDE1	ENST00000564172.1	c.*141A>G		3_prime_UTR_variant, NMD_transcript_variant	3/6	1		ENSP00000457431
GDE1	ENST00000569899.5	c.190A>G	p.Arg64Gly	missense_variant	2/4	4		ENSP00000456295
GDE1	ENST00000569773.1	c.142A>G	p.Arg48Gly	missense_variant	3/4	3		ENSP00000454755

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

The c.472A>G (p.R158G) alteration is located in exon 3 (coding exon 3) of the GDE1 gene. This alteration results from a A to G substitution at nucleotide position 472, causing the arginine (R) at amino acid position 158 to be replaced by a glycine (G). 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	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	0.86	N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N;.;N
REVEL	Benign	0.10
Sift	Benign	0.11	T;.;T
Sift4G	Benign	0.10	T;T;.
Polyphen		0.17	B;.;.
Vest4		0.41
MutPred		0.55		Loss of helix (P = 0.1299);.;.;
MVP		0.31
MPC		0.29
ClinPred		0.49	T
GERP RS		2.4
Varity_R		0.088
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-19522232;