Variant chr21-37065618-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_153682.3(PIGP):c.369C>T(p.Phe123Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,613,284 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 43 hom. )

Consequence

PIGP
NM_153682.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.657

Variant links:

Genes affected

PIGP (HGNC:3046): (phosphatidylinositol glycan anchor biosynthesis class P) This gene encodes an enzyme involved in the first step of glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells that serves to anchor proteins to the cell surface. The encoded protein is a component of the GPI-N-acetylglucosaminyltransferase complex that catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). This gene is located in the Down Syndrome critical region on chromosome 21 and is a candidate for the pathogenesis of Down syndrome. This gene has multiple pseudogenes and is a member of the phosphatidylinositol glycan anchor biosynthesis gene family. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]

PIGP links:

PIGP (HGNC:):

PIGP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 21-37065618-G-A is Benign according to our data. Variant chr21-37065618-G-A is described in ClinVar as [Benign]. Clinvar id is 713319.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.657 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGP	NM_153682.3 linkuse as main transcript	c.369C>T	p.Phe123Phe	synonymous_variant	5/5	ENST00000360525.9	NP_710149.1	P57054-2
PIGP	NM_153681.2 linkuse as main transcript	c.441C>T	p.Phe147Phe	synonymous_variant	4/4		NP_710148.1	P57054-1
PIGP	NM_001320480.2 linkuse as main transcript	c.369C>T	p.Phe123Phe	synonymous_variant	5/5		NP_001307409.1	P57054-2
PIGP	NM_016430.4 linkuse as main transcript	c.291C>T	p.Phe97Phe	synonymous_variant	6/6		NP_057514.2	P57054-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGP	ENST00000360525.9 linkuse as main transcript	c.369C>T	p.Phe123Phe	synonymous_variant	5/5	1	NM_153682.3	ENSP00000353719.3		P57054-2

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

484

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0175

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0329

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00475

AC:

1184

AN:

249510

Hom.:

AF XY:

0.00457

AC XY:

617

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.0174

Gnomad SAS exome

AF:

0.000557

Gnomad FIN exome

AF:

0.0331

Gnomad NFE exome

AF:

0.000962

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00185

AC:

2704

AN:

1461056

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1346

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0130

Gnomad4 SAS exome

AF:

0.000929

Gnomad4 FIN exome

AF:

0.0316

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.00196

GnomAD4 genome

AF:

0.00317

AC:

483

AN:

152228

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

366

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0176

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0329

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000887

Hom.:

Bravo

AF:

0.000963

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

8.7

DANN

Benign

0.67

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

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