1-155235003-G-T

Position:

• chr1-155235003-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM5 BP4

The NM_000157.4(GBA1):​c.1603C>A​(p.Arg535Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R535C) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 11)
• Consequence: GBA1 NM_000157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-155235003-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 242383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.3450405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBA1	NM_000157.4	c.1603C>A	p.Arg535Ser	missense_variant	11/11	ENST00000368373.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBA1	ENST00000368373.8	c.1603C>A	p.Arg535Ser	missense_variant	11/11	1	NM_000157.4	P1

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 9

GnomAD4 genome Cov.: 11

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.42	T;T;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.90	.;D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.26	N;N;.;.
MutationTaster	Benign	0.91	N;N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.85	P;P;.;.
Vest4		0.42
MutPred		0.28		Loss of MoRF binding (P = 0.0179);Loss of MoRF binding (P = 0.0179);.;.;
MVP		0.89
MPC		1.3
ClinPred		0.47	T
GERP RS		3.2
Varity_R		0.49
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155204794;