Variant 14-67587182-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4BS1BS2

The NM_020715.3(PLEKHH1):c.4042C>T(p.Arg1348Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 1,613,694 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 95 hom. )

Consequence

PLEKHH1
NM_020715.3 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.294

Variant links:

Genes affected

PLEKHH1 (HGNC:17733): (pleckstrin homology, MyTH4 and FERM domain containing H1) Predicted to be located in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHH1 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM4

Stoplost variant in NM_020715.3 Downstream stopcodon found after 1411 codons.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00811 (11855/1461444) while in subpopulation MID AF= 0.0248 (143/5766). AF 95% confidence interval is 0.0215. There are 95 homozygotes in gnomad4_exome. There are 5786 alleles in male gnomad4_exome subpopulation. Median coverage is 37. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHH1	NM_020715.3 linkuse as main transcript	c.4042C>T	p.Arg1348Ter	stop_gained	29/29	ENST00000329153.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHH1	ENST00000329153.10 linkuse as main transcript	c.4042C>T	p.Arg1348Ter	stop_gained	29/29	1	NM_020715.3	P1	Q9ULM0-1

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

927

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.0423

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00844

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00769

AC:

1916

AN:

249222

Hom.:

AF XY:

0.00773

AC XY:

1045

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00510

Gnomad ASJ exome

AF:

0.0422

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.00952

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.00811

AC:

11855

AN:

1461444

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

5786

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00530

Gnomad4 ASJ exome

AF:

0.0403

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00339

Gnomad4 FIN exome

AF:

0.00191

Gnomad4 NFE exome

AF:

0.00849

Gnomad4 OTH exome

AF:

0.00904

GnomAD4 genome

AF:

0.00608

AC:

926

AN:

152250

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

432

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.0423

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00844

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00609

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.0117

AC:

ExAC

AF:

0.00757

AC:

915

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0109

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.54

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.25

MutationTaster

Benign

1.0

D;N

Vest4

0.029

ClinPred

0.094

GERP RS

3.1

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