NM_001503.4:c.1870G>T

Variant names:

• chr6-24445782-C-A
• rs201973866
• NM_001503.4:c.1870G>T

Variant summary

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

The NM_001503.4(GPLD1):​c.1870G>T​(p.Val624Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPLD1 NM_001503.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.1870G>T	p.Val624Leu	missense_variant	Exon 19 of 25	ENST00000230036.2	NP_001494.2
GPLD1	XM_017010753.3	c.1900G>T	p.Val634Leu	missense_variant	Exon 20 of 26		XP_016866242.1
GPLD1	XM_047418657.1	c.1381G>T	p.Val461Leu	missense_variant	Exon 14 of 20		XP_047274613.1
GPLD1	XR_007059240.1	n.2177G>T		non_coding_transcript_exon_variant	Exon 20 of 27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.1870G>T	p.Val624Leu	missense_variant	Exon 19 of 25	1	NM_001503.4	ENSP00000230036.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.29
Sift	Benign	0.073	T
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.42		Loss of ubiquitination at K619 (P = 0.1062);
MVP		0.72
MPC		0.45
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.18
gMVP		0.67

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

Other links and lift over

dbSNP: rs201973866; hg19: chr6-24446010;