NM_001503.4:c.2442delA

Variant names:

• chr6-24429112-CT-C
• rs573778305
• NM_001503.4:c.2442delA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001503.4(GPLD1):​c.2442delA​(p.Val815SerfsTer47) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,611,400 control chromosomes in the GnomAD database, including 40 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (37 hom.)
• Consequence: GPLD1 NM_001503.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.420

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-24429112-CT-C is Benign according to our data. Variant chr6-24429112-CT-C is described in ClinVar as [Benign]. Clinvar id is 730949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPLD1	NM_001503.4	c.2442delA	p.Val815SerfsTer47	frameshift_variant	Exon 25 of 25	ENST00000230036.2	NP_001494.2
GPLD1	XM_017010753.3	c.2472delA	p.Val825SerfsTer47	frameshift_variant	Exon 26 of 26		XP_016866242.1
GPLD1	XM_047418657.1	c.1953delA	p.Val652SerfsTer47	frameshift_variant	Exon 20 of 20		XP_047274613.1
GPLD1	XR_007059240.1	n.2749delA		non_coding_transcript_exon_variant	Exon 26 of 27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPLD1	ENST00000230036.2	c.2442delA	p.Val815SerfsTer47	frameshift_variant	Exon 25 of 25	1	NM_001503.4	ENSP00000230036.1
GPLD1	ENST00000492917.2	n.317delA		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 573 AN: 152212 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00453 AC: 1138 AN: 251130 Hom.: 8 AF XY: 0.00441 AC XY: 598 AN XY: 135752

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0211

Gnomad NFE exome AF: 0.00504

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00418 AC: 6095 AN: 1459070 Hom.: 37 Cov.: 28 AF XY: 0.00407 AC XY: 2952 AN XY: 726110

Gnomad4 AFR exome AF: 0.000629

Gnomad4 AMR exome AF: 0.000895

Gnomad4 ASJ exome AF: 0.00329

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.00416

Gnomad4 OTH exome AF: 0.00418

GnomAD4 genome AF: 0.00376 AC: 573 AN: 152330 Hom.: 3 Cov.: 32 AF XY: 0.00438 AC XY: 326 AN XY: 74500

Gnomad4 AFR AF: 0.000697

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.00400

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00121 Hom.: 2

Bravo AF: 0.00229

EpiCase AF: 0.00284

EpiControl AF: 0.00302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs573778305; hg19: chr6-24429340;