16-19503482-T-G

Position:

chr16-19503482-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016641.4(GDE1):c.984A>C(p.Glu328Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E328K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

GDE1
NM_016641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.84

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:

GDE1 (HGNC:):

GDE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018150479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDE1	NM_016641.4 linkuse as main transcript	c.984A>C	p.Glu328Asp	missense_variant	6/6	ENST00000353258.8	NP_057725.1	Q9NZC3
GDE1	NM_001324067.2 linkuse as main transcript	c.891A>C	p.Glu297Asp	missense_variant	5/5		NP_001310996.1
GDE1	NM_001324066.2 linkuse as main transcript	c.654A>C	p.Glu218Asp	missense_variant	6/6		NP_001310995.1	A0A024QYU1
GDE1	NR_136689.2 linkuse as main transcript	n.1150A>C		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GDE1	ENST00000353258.8 linkuse as main transcript	c.984A>C	p.Glu328Asp	missense_variant	6/6	1	NM_016641.4	ENSP00000261386.3	Q9NZC3
GDE1	ENST00000564172.1 linkuse as main transcript	n.*653A>C		non_coding_transcript_exon_variant	6/6	1		ENSP00000457431.1	H3BU22
GDE1	ENST00000564172.1 linkuse as main transcript	n.*653A>C		3_prime_UTR_variant	6/6	1		ENSP00000457431.1	H3BU22
GDE1	ENST00000563645.1 linkuse as main transcript	n.388A>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251086

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151798

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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

Sep 20, 2023

The c.984A>C (p.E328D) alteration is located in exon 6 (coding exon 6) of the GDE1 gene. This alteration results from a A to C substitution at nucleotide position 984, causing the glutamic acid (E) at amino acid position 328 to be replaced by an aspartic acid (D). 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

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.9

DANN

Benign

0.76

DEOGEN2

Benign

0.013

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.64

M_CAP

Benign

0.0024

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

0.68

REVEL

Benign

0.022

Sift

Benign

0.93

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.030

MutPred

0.17

Loss of disorder (P = 0.2254);

MVP

0.14

MPC

0.17

ClinPred

0.020

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.39

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