Variant 19-11436188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001289104.2(PRKCSH):c.71C>T(p.Ser24Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000418 in 1,436,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

PRKCSH
NM_001289104.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Variant links:

Genes affected

PRKCSH (HGNC:9411): (PRKCSH beta subunit of glucosidase II) This gene encodes the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum. The encoded protein is an acidic phosphoprotein known to be a substrate for protein kinase C. Mutations in this gene have been associated with the autosomal dominant polycystic liver disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

PRKCSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2 linkuse as main transcript	c.71C>T	p.Ser24Phe	missense_variant	2/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1 linkuse as main transcript	c.71C>T	p.Ser24Phe	missense_variant	2/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000499

AC:

AN:

200588

Hom.:

AF XY:

0.00000918

AC XY:

AN XY:

108934

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:

0.00

Gnomad FIN exome

AF:

0.0000580

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000418

AC:

AN:

1436466

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713096

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:

0.00

Gnomad4 FIN exome

AF:

0.0000198

Gnomad4 NFE exome

AF:

0.00000454

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.71C>T (p.S24F) alteration is located in exon 2 (coding exon 1) of the PRKCSH gene. This alteration results from a C to T substitution at nucleotide position 71, causing the serine (S) at amino acid position 24 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

.;T;.;T;T;T;T;.;T

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.95

.;D;D;T;D;D;D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.67

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.28

MutationAssessor

Uncertain

2.5

M;.;.;.;.;.;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.69

Sift4G

Uncertain

0.014

D;D;D;D;D;D;D;D;D

Polyphen

1.0

.;.;.;.;.;.;.;.;D

Vest4

0.61

MutPred

0.45

Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);

MVP

0.87

ClinPred

0.89

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.56

gMVP

0.53

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