Genetic Variant GPD1L:p.Pro5Leu (chr3-32106725-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015141.4(GPD1L):c.14C>T(p.Pro5Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P5S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GPD1L
NM_015141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

Publications

0 publications found

Variant links:

Genes affected

GPD1L (HGNC:28956): (glycerol-3-phosphate dehydrogenase 1 like) The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]

GPD1L Gene-Disease associations (from GenCC):

Brugada syndrome 2
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

GPD1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3942453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1L	NM_015141.4	MANE Select	c.14C>T	p.Pro5Leu	missense	Exon 1 of 8	NP_055956.1	Q8N335

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPD1L	ENST00000282541.10	TSL:1 MANE Select	c.14C>T	p.Pro5Leu	missense	Exon 1 of 8	ENSP00000282541.6	Q8N335
GPD1L	ENST00000902849.1		c.14C>T	p.Pro5Leu	missense	Exon 1 of 8	ENSP00000572908.1
GPD1L	ENST00000902848.1		c.14C>T	p.Pro5Leu	missense	Exon 1 of 7	ENSP00000572907.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

196744

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1411472

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701942

African (AFR)

AF:

0.00

AC:

AN:

29246

American (AMR)

AF:

0.00

AC:

AN:

39444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24558

East Asian (EAS)

AF:

0.00

AC:

AN:

34034

South Asian (SAS)

AF:

0.00

AC:

AN:

81080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5556

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088136

Other (OTH)

AF:

0.00

AC:

AN:

57852

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Brugada syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Benign

-0.049

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

PhyloP100

4.0

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.12

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0070

Polyphen

0.0050

Vest4

0.31

MutPred

0.51

Loss of disorder (P = 0.0307)

MVP

0.59

MPC

0.41

ClinPred

0.98

GERP RS

4.4

PromoterAI

0.029

Neutral

(source)

Varity_R

0.70

gMVP

0.71

Mutation Taster

=53/47

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over