Variant chr12-109880370-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_016433.4(GLTP):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000146 in 1,573,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

GLTP
NM_016433.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

GLTP (HGNC:24867): (glycolipid transfer protein) The protein encoded by this gene is similar to bovine and porcine proteins which accelerate transfer of certain glycosphingolipids and glyceroglycolipids between membranes. It is thought to be a cytoplasmic protein. [provided by RefSeq, Jul 2008]

GLTP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a modified_residue N-acetylalanine (size 0) in uniprot entity GLTP_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.329077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLTP	NM_016433.4 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/5	ENST00000318348.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLTP	ENST00000318348.9 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/5	1	NM_016433.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000148

AC:

AN:

1421518

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

707784

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

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:

0.0000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151556

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73974

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

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

Sep 29, 2023

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the GLTP gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 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

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.85

T;T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.6

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.092

Sift

Uncertain

0.011

D;D;.

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.15

B;.;.

Vest4

0.51

MutPred

0.36

Gain of catalytic residue at E6 (P = 0.0028);Gain of catalytic residue at E6 (P = 0.0028);Gain of catalytic residue at E6 (P = 0.0028);

MVP

0.39

MPC

0.36

ClinPred

0.56

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.42

gMVP

0.74

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