16-19517015-T-C

Position:

chr16-19517015-T-C

Variant summary

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

The ENST00000353258.8(GDE1):c.436A>G(p.Arg146Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,613,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

GDE1
ENST00000353258.8 missense, splice_region

Scores

Splicing: ADA: 0.9868

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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=0.15021604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GDE1	NM_016641.4 linkuse as main transcript	c.436A>G	p.Arg146Gly	missense_variant, splice_region_variant	2/6	ENST00000353258.8	NP_057725.1
GDE1	NM_001324067.2 linkuse as main transcript	c.436A>G	p.Arg146Gly	missense_variant, splice_region_variant	2/5		NP_001310996.1
GDE1	NM_001324066.2 linkuse as main transcript	c.106A>G	p.Arg36Gly	missense_variant, splice_region_variant	2/6		NP_001310995.1
GDE1	NR_136689.2 linkuse as main transcript	n.570A>G		splice_region_variant, non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GDE1	ENST00000353258.8 linkuse as main transcript	c.436A>G	p.Arg146Gly	missense_variant, splice_region_variant	2/6	1	NM_016641.4	ENSP00000261386	P1
GDE1	ENST00000564172.1 linkuse as main transcript	c.*105A>G		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	2/6	1		ENSP00000457431
GDE1	ENST00000569899.5 linkuse as main transcript	c.154A>G	p.Arg52Gly	missense_variant, splice_region_variant	1/4	4		ENSP00000456295
GDE1	ENST00000569773.1 linkuse as main transcript	c.106A>G	p.Arg36Gly	missense_variant, splice_region_variant	2/4	3		ENSP00000454755

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152198

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:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000159

AC:

AN:

251162

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.0000463

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000220

AC:

322

AN:

1461008

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

165

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000105

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

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:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000110

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

Jul 07, 2022

The c.436A>G (p.R146G) alteration is located in exon 2 (coding exon 2) of the GDE1 gene. This alteration results from a A to G substitution at nucleotide position 436, causing the arginine (R) at amino acid position 146 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;T

Eigen

Benign

-0.081

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

D;.;D

REVEL

Benign

0.13

Sift

Benign

0.050

D;.;D

Sift4G

Benign

0.47

T;T;.

Polyphen

0.54

P;.;.

Vest4

0.36

MVP

0.47

MPC

0.51

ClinPred

0.099

GERP RS

4.4

Varity_R

0.15

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.69

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