Variant 1-235342723-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP5BP4

The ENST00000282841.9(GGPS1):c.854T>G(p.Val285Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

GGPS1
ENST00000282841.9 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

GGPS1 (HGNC:4249): (geranylgeranyl diphosphate synthase 1) This gene is a member of the prenyltransferase family and encodes a protein with geranylgeranyl diphosphate (GGPP) synthase activity. The enzyme catalyzes the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. GGPP is an important molecule responsible for the C20-prenylation of proteins and for the regulation of a nuclear hormone receptor. Alternate transcriptional splice variants, both protein-coding and non-protein-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

GGPS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a chain Geranylgeranyl pyrophosphate synthase (size 299) in uniprot entity GGPPS_HUMAN there are 12 pathogenic changes around while only 0 benign (100%) in ENST00000282841.9

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-235342723-T-G is Pathogenic according to our data. Variant chr1-235342723-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1232305.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.22674015). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGPS1	NM_004837.4 linkuse as main transcript	c.854T>G	p.Val285Gly	missense_variant	4/4	ENST00000282841.9	NP_004828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGPS1	ENST00000282841.9 linkuse as main transcript	c.854T>G	p.Val285Gly	missense_variant	4/4	1	NM_004837.4	ENSP00000282841	P1	O95749-1
GGPS1	ENST00000488594.5 linkuse as main transcript	c.854T>G	p.Val285Gly	missense_variant	4/4	1		ENSP00000418690	P1	O95749-1
GGPS1	ENST00000358966.6 linkuse as main transcript	c.854T>G	p.Val285Gly	missense_variant	4/4	2		ENSP00000351852	P1	O95749-1
GGPS1	ENST00000391855.2 linkuse as main transcript	c.692T>G	p.Val231Gly	missense_variant	3/3	2		ENSP00000375728		O95749-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.16

T;T;T;.

Eigen

Benign

-0.0086

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

.;T;.;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.2

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Uncertain

0.29

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.21

B;B;B;.

Vest4

0.28

MutPred

0.41

Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);.;

MVP

0.34

MPC

0.59

ClinPred

0.84

GERP RS

5.0

Varity_R

0.40

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over