12-109880353-A-C

Position:

• chr12-109880353-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016433.4(GLTP):​c.22T>G​(p.Leu8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GLTP NM_016433.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.842

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]

ACMG classification

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=0.09090689).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLTP	NM_016433.4	c.22T>G	p.Leu8Val	missense_variant	1/5	ENST00000318348.9	NP_057517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLTP	ENST00000318348.9	c.22T>G	p.Leu8Val	missense_variant	1/5	1	NM_016433.4	ENSP00000315263.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.22T>G (p.L8V) alteration is located in exon 1 (coding exon 1) of the GLTP gene. This alteration results from a T to G substitution at nucleotide position 22, causing the leucine (L) at amino acid position 8 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	0.086
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.27	T;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.26	N;N;.
REVEL	Benign	0.077
Sift	Benign	0.32	T;T;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.20
MutPred		0.48		Gain of catalytic residue at K10 (P = 0.0319);Gain of catalytic residue at K10 (P = 0.0319);Gain of catalytic residue at K10 (P = 0.0319);
MVP		0.13
MPC		0.35
ClinPred		0.54	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-110318158;