Variant 1-155234895-TGGCCCTGCTGTGCCCTCTTTAGTCACAGACAGCGTGTGAGCTGACTCTGTCCCTTTAATGCCCAGGCTGAGCCCAGTGCCTCCTTGAGTATCTGCTCCATCACTGGCGACGCCACAGGTAGGTGTGAATGGAGTAGCCAGGTGAGATTGTCTCCAGGAAGCCCACAGCA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate

The NM_000157.4(GBA1):c.1542_*99del variant causes a stop lost, 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 4)

Consequence

GBA1
NM_000157.4 stop_lost, 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.52

Variant links:

Genes affected

GBA1 (HGNC:4177): (glucosylceramidase beta 1) This gene encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism. Mutations in this gene cause Gaucher disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides. A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

GBA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Stoplost variant. No alternative stopcodon identified downstream, so we assume a Nonstop Mediated Decay. LoF is a known mechanism of disease.

PP5

Variant 1-155234895-TGGCCCTGCTGTGCCCTCTTTAGTCACAGACAGCGTGTGAGCTGACTCTGTCCCTTTAATGCCCAGGCTGAGCCCAGTGCCTCCTTGAGTATCTGCTCCATCACTGGCGACGCCACAGGTAGGTGTGAATGGAGTAGCCAGGTGAGATTGTCTCCAGGAAGCCCACAGCA-T is Pathogenic according to our data. Variant chr1-155234895-TGGCCCTGCTGTGCCCTCTTTAGTCACAGACAGCGTGTGAGCTGACTCTGTCCCTTTAATGCCCAGGCTGAGCCCAGTGCCTCCTTGAGTATCTGCTCCATCACTGGCGACGCCACAGGTAGGTGTGAATGGAGTAGCCAGGTGAGATTGTCTCCAGGAAGCCCACAGCA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2440413.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBA1	NM_000157.4 linkuse as main transcript	c.1542_*99del		stop_lost, 3_prime_UTR_variant	11/11	ENST00000368373.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBA1	ENST00000368373.8 linkuse as main transcript	c.1542_*99del		stop_lost, 3_prime_UTR_variant	11/11	1	NM_000157.4	P1	P04062-1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.