Variant 14-67600254-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004569.5(PIGH):c.-51C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,442,662 control chromosomes in the GnomAD database, including 17,420 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2058 hom., cov: 34)

Exomes 𝑓: 0.15 ( 15362 hom. )

Consequence

PIGH
NM_004569.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.39

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:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGH	NM_004569.5 link	c.-51C>G		5_prime_UTR_variant	1/4	ENST00000216452.9	NP_004560.1	Q14442

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGH	ENST00000216452.9 link	c.-51C>G		5_prime_UTR_variant	1/4	1	NM_004569.5	ENSP00000216452.4		Q14442

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22178

AN:

152072

Hom.:

2055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0728

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.211

AC:

15616

AN:

73944

Hom.:

2079

AF XY:

0.207

AC XY:

8288

AN XY:

39986

show subpopulations

Gnomad AFR exome

AF:

0.0691

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.296

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.146

AC:

187791

AN:

1290474

Hom.:

15362

Cov.:

AF XY:

0.147

AC XY:

93298

AN XY:

632824

show subpopulations

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.253

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.146

AC:

22192

AN:

152188

Hom.:

2058

Cov.:

AF XY:

0.152

AC XY:

11307

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0726

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.0888

Hom.:

265

Bravo

AF:

0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.49

DANN

Benign

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over