Variant 14-67593857-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_004569.5(PIGH):c.276C>T(p.Ile92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 1,611,808 control chromosomes in the GnomAD database, including 7,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.091 ( 672 hom., cov: 32)

Exomes 𝑓: 0.091 ( 6435 hom. )

Consequence

PIGH
NM_004569.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

PIGH (HGNC:8964): (phosphatidylinositol glycan anchor biosynthesis class H) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. The protein encoded by this gene is a subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

PIGH links:

GPHN (HGNC:):

GPHN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 14-67593857-G-A is Benign according to our data. Variant chr14-67593857-G-A is described in ClinVar as [Benign]. Clinvar id is 3056965.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGH	NM_004569.5 linkuse as main transcript	c.276C>T	p.Ile92=	synonymous_variant	2/4	ENST00000216452.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGH	ENST00000216452.9 linkuse as main transcript	c.276C>T	p.Ile92=	synonymous_variant	2/4	1	NM_004569.5	P4

Frequencies

GnomAD3 genomes

AF:

0.0911

AC:

13845

AN:

152034

Hom.:

669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0932

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0691

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0242

Gnomad SAS

AF:

0.0490

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0991

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.0843

AC:

21178

AN:

251264

Hom.:

1025

AF XY:

0.0834

AC XY:

11324

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0910

Gnomad AMR exome

AF:

0.0640

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.0242

Gnomad SAS exome

AF:

0.0528

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0989

Gnomad OTH exome

AF:

0.0948

GnomAD4 exome

AF:

0.0911

AC:

133008

AN:

1459656

Hom.:

6435

Cov.:

AF XY:

0.0905

AC XY:

65748

AN XY:

726222

show subpopulations

Gnomad4 AFR exome

AF:

0.0952

Gnomad4 AMR exome

AF:

0.0664

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.0306

Gnomad4 SAS exome

AF:

0.0543

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.0953

Gnomad4 OTH exome

AF:

0.0882

GnomAD4 genome

AF:

0.0912

AC:

13869

AN:

152152

Hom.:

672

Cov.:

AF XY:

0.0891

AC XY:

6629

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0934

Gnomad4 AMR

AF:

0.0692

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0245

Gnomad4 SAS

AF:

0.0501

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.0991

Gnomad4 OTH

AF:

0.0987

Alfa

AF:

0.0968

Hom.:

343

Bravo

AF:

0.0898

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

EpiCase

AF:

0.100

EpiControl

AF:

0.0999

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PIGH-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.70

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