Variant 16-19521790-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016641.4(GDE1):c.175C>T(p.Leu59Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000263 in 152,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Consequence

GDE1
NM_016641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3549474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDE1	NM_016641.4 linkuse as main transcript	c.175C>T	p.Leu59Phe	missense_variant	1/6	ENST00000353258.8	NP_057725.1	Q9NZC3
GDE1	NM_001324067.2 linkuse as main transcript	c.175C>T	p.Leu59Phe	missense_variant	1/5		NP_001310996.1
GDE1	NM_001324066.2 linkuse as main transcript	c.-152C>T		5_prime_UTR_variant	1/6		NP_001310995.1	A0A024QYU1
GDE1	NR_136689.2 linkuse as main transcript	n.309C>T		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.175C>T	p.Leu59Phe	missense_variant	1/6	1	NM_016641.4	ENSP00000261386.3		Q9NZC3
GDE1	ENST00000564172.1 linkuse as main transcript	n.175C>T		non_coding_transcript_exon_variant	1/6	1		ENSP00000457431.1		H3BU22

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00143

Bravo

AF:

0.0000189

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

Jun 18, 2021

The c.175C>T (p.L59F) alteration is located in exon 1 (coding exon 1) of the GDE1 gene. This alteration results from a C to T substitution at nucleotide position 175, causing the leucine (L) at amino acid position 59 to be replaced by a phenylalanine (F). 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

0.26

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

M_CAP

Benign

0.0077

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.5

REVEL

Benign

0.15

Sift

Benign

0.10

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.44

MutPred

0.35

Gain of methylation at K60 (P = 0.0374);

MVP

0.38

MPC

0.59

ClinPred

0.95

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.31

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over