Variant 16-19521870-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000353258.8(GDE1):c.95G>C(p.Cys32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,605,900 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

GDE1
ENST00000353258.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15124953).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GDE1	NM_016641.4 linkuse as main transcript	c.95G>C	p.Cys32Ser	missense_variant	1/6	ENST00000353258.8	NP_057725.1
GDE1	NM_001324067.2 linkuse as main transcript	c.95G>C	p.Cys32Ser	missense_variant	1/5		NP_001310996.1
GDE1	NM_001324066.2 linkuse as main transcript	c.-232G>C		5_prime_UTR_variant	1/6		NP_001310995.1
GDE1	NR_136689.2 linkuse as main transcript	n.229G>C		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.95G>C	p.Cys32Ser	missense_variant	1/6	1	NM_016641.4	ENSP00000261386	P1
GDE1	ENST00000564172.1 linkuse as main transcript	c.95G>C	p.Cys32Ser	missense_variant, NMD_transcript_variant	1/6	1		ENSP00000457431

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000264

AC:

AN:

227248

Hom.:

AF XY:

0.000291

AC XY:

AN XY:

123730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000309

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000244

Gnomad FIN exome

AF:

0.000101

Gnomad NFE exome

AF:

0.000408

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000357

AC:

519

AN:

1453692

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

276

AN XY:

722428

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000254

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000413

Gnomad4 FIN exome

AF:

0.0000575

Gnomad4 NFE exome

AF:

0.000392

Gnomad4 OTH exome

AF:

0.000533

GnomAD4 genome

AF:

0.000223

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000219

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000256

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

Feb 06, 2023

The c.95G>C (p.C32S) alteration is located in exon 1 (coding exon 1) of the GDE1 gene. This alteration results from a G to C substitution at nucleotide position 95, causing the cysteine (C) at amino acid position 32 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

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.063

Eigen

Benign

-0.051

Eigen_PC

Benign

0.070

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.64

M_CAP

Benign

0.0043

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.74

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.5

REVEL

Benign

0.091

Sift

Benign

0.37

Sift4G

Benign

0.64

Polyphen

0.52

Vest4

0.29

MutPred

0.59

Loss of stability (P = 0.0025);

MVP

0.29

MPC

0.24

ClinPred

0.079

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.76

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