rs587777643

Variant names:

• chr8-143215283-C-A
• NM_178172.6:c.320C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-143215283-C-A
• chr8-143215283-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_178172.6(GPIHBP1):​c.320C>A​(p.Ser107Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPIHBP1 NM_178172.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

Genes affected

GPIHBP1 (HGNC:24945): (glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1) This gene encodes a capillary endothelial cell protein that facilitates the lipolytic processing of triglyceride-rich lipoproteins. The encoded protein is a glycosylphosphatidylinositol-anchored protein that is a member of the lymphocyte antigen 6 (Ly6) family. This protein plays a major role in transporting lipoprotein lipase (LPL) from the subendothelial spaces to the capillary lumen. Mutations in this gene are the cause of hyperlipoproteinemia, type 1D. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a mutagenesis_site Promotes formation of dimers and oligomers reducing number of monomers. (size 0) in uniprot entity HDBP1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPIHBP1	NM_178172.6	c.320C>A	p.Ser107Tyr	missense_variant	Exon 4 of 4	ENST00000622500.2	NP_835466.2
GPIHBP1	NM_001301772.2	c.320C>A	p.Ser107Tyr	missense_variant	Exon 4 of 5		NP_001288701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPIHBP1	ENST00000622500.2	c.320C>A	p.Ser107Tyr	missense_variant	Exon 4 of 4	1	NM_178172.6	ENSP00000480053.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460682 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.32	D
PrimateAI	Benign	0.37	T
Sift4G	Pathogenic	0.0	D
Vest4		0.54
MutPred		0.61		Loss of disorder (P = 0.0034);
MVP		0.82
ClinPred		0.93	D
GERP RS		4.2
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr8-144297158;