Variant 16-19521754-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016641.4(GDE1):c.211C>G(p.Arg71Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GDE1
NM_016641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

Variant links:

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]

GDE1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDE1	NM_016641.4 linkuse as main transcript	c.211C>G	p.Arg71Gly	missense_variant	1/6	ENST00000353258.8	NP_057725.1	Q9NZC3
GDE1	NM_001324067.2 linkuse as main transcript	c.211C>G	p.Arg71Gly	missense_variant	1/5		NP_001310996.1
GDE1	NM_001324066.2 linkuse as main transcript	c.-116C>G		5_prime_UTR_variant	1/6		NP_001310995.1	A0A024QYU1
GDE1	NR_136689.2 linkuse as main transcript	n.345C>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDE1	ENST00000353258.8 linkuse as main transcript	c.211C>G	p.Arg71Gly	missense_variant	1/6	1	NM_016641.4	ENSP00000261386.3		Q9NZC3
GDE1	ENST00000564172.1 linkuse as main transcript	n.211C>G		non_coding_transcript_exon_variant	1/6	1		ENSP00000457431.1		H3BU22

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459550

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.211C>G (p.R71G) alteration is located in exon 1 (coding exon 1) of the GDE1 gene. This alteration results from a C to G substitution at nucleotide position 211, causing the arginine (R) at amino acid position 71 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.8

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.63

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.031

Polyphen

1.0

Vest4

0.92

MutPred

0.87

Loss of methylation at R71 (P = 0.0207);

MVP

0.84

MPC

0.86

ClinPred

1.0

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.89

gMVP

0.99

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over