Variant 6-24446974-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_001503.4(GPLD1):c.1684C>G(p.Leu562Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,613,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

GPLD1
NM_001503.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

GPLD1 (HGNC:4459): (glycosylphosphatidylinositol specific phospholipase D1) Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]

GPLD1 links:

GPLD1 (HGNC:):

GPLD1 links:

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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=0.26373917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPLD1	NM_001503.4 linkuse as main transcript	c.1684C>G	p.Leu562Val	missense_variant	18/25	ENST00000230036.2	NP_001494.2	P80108-1
GPLD1	XM_017010753.3 linkuse as main transcript	c.1714C>G	p.Leu572Val	missense_variant	19/26		XP_016866242.1
GPLD1	XM_047418657.1 linkuse as main transcript	c.1195C>G	p.Leu399Val	missense_variant	13/20		XP_047274613.1
GPLD1	XR_007059240.1 linkuse as main transcript	n.1991C>G		non_coding_transcript_exon_variant	19/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2 linkuse as main transcript	c.1684C>G	p.Leu562Val	missense_variant	18/25	1	NM_001503.4	ENSP00000230036.1		P80108-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.000191

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000280

AC:

AN:

250334

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000849

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:

0.000282

Gnomad OTH exome

AF:

0.000822

GnomAD4 exome

AF:

0.000244

AC:

356

AN:

1460902

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

156

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000807

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:

0.000246

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000256

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

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 13, 2021

The c.1684C>G (p.L562V) alteration is located in exon 18 (coding exon 18) of the GPLD1 gene. This alteration results from a C to G substitution at nucleotide position 1684, causing the leucine (L) at amino acid position 562 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

0.15

Eigen_PC

Benign

-0.0011

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.072

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

0.96

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.50

MVP

0.77

MPC

0.39

ClinPred

0.097

GERP RS

4.5

Varity_R

0.13

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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