Variant rs761543313 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_004569.5(PIGH):c.1A>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000127 in 1,420,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

PIGH
NM_004569.5 start_lost

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.77

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 Pathogenic. Variant got 11 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-67600203-T-A is Pathogenic according to our data. Variant chr14-67600203-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 545630.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-67600203-T-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGH	NM_004569.5 linkuse as main transcript	c.1A>T	p.Met1?	start_lost	1/4	ENST00000216452.9	NP_004560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGH	ENST00000216452.9 linkuse as main transcript	c.1A>T	p.Met1?	start_lost	1/4	1	NM_004569.5	ENSP00000216452	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000225

AC:

AN:

177418

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

97198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000159

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000127

AC:

AN:

1420360

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

703600

show subpopulations

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:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000257

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Glycosylphosphatidylinositol biosynthesis defect 17

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.033

T;T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Pathogenic

0.69

MetaRNN

Pathogenic

0.84

D;D;D;D

MetaSVM

Uncertain

-0.24

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Benign

-0.47

N;N;N;N

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.70

P;.;.;.

Vest4

0.85

MutPred

0.68

Gain of loop (P = 0.4248);Gain of loop (P = 0.4248);Gain of loop (P = 0.4248);Gain of loop (P = 0.4248);

MVP

0.75

ClinPred

0.98

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.87

gMVP

0.54

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

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