Variant 16-19503558-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016641.4(GDE1):c.908C>G(p.Thr303Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,460,628 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GDE1
NM_016641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1109969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDE1	NM_016641.4 linkuse as main transcript	c.908C>G	p.Thr303Ser	missense_variant	6/6	ENST00000353258.8	NP_057725.1	Q9NZC3
GDE1	NM_001324067.2 linkuse as main transcript	c.815C>G	p.Thr272Ser	missense_variant	5/5		NP_001310996.1
GDE1	NM_001324066.2 linkuse as main transcript	c.578C>G	p.Thr193Ser	missense_variant	6/6		NP_001310995.1	A0A024QYU1
GDE1	NR_136689.2 linkuse as main transcript	n.1074C>G		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.908C>G	p.Thr303Ser	missense_variant	6/6	1	NM_016641.4	ENSP00000261386.3	Q9NZC3
GDE1	ENST00000564172.1 linkuse as main transcript	n.*577C>G		non_coding_transcript_exon_variant	6/6	1		ENSP00000457431.1	H3BU22
GDE1	ENST00000564172.1 linkuse as main transcript	n.*577C>G		3_prime_UTR_variant	6/6	1		ENSP00000457431.1	H3BU22
GDE1	ENST00000563645.1 linkuse as main transcript	n.312C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251406

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135868

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:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1460628

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726738

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:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Dec 04, 2024

The c.908C>G (p.T303S) alteration is located in exon 6 (coding exon 6) of the GDE1 gene. This alteration results from a C to G substitution at nucleotide position 908, causing the threonine (T) at amino acid position 303 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.022

Eigen

Benign

0.016

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.66

M_CAP

Benign

0.0071

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.70

REVEL

Benign

0.13

Sift

Benign

0.60

Sift4G

Benign

0.48

Polyphen

0.34

Vest4

0.066

MutPred

0.40

Loss of loop (P = 0.0374);

MVP

0.21

MPC

0.20

ClinPred

0.094

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.58

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