chr1-235342723-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_004837.4(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
NM_004837.4 missense
NM_004837.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 2.50
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
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 | UniProt |
---|---|---|---|---|---|---|---|
GGPS1 | NM_004837.4 | c.854T>G | p.Val285Gly | missense_variant | 4/4 | ENST00000282841.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GGPS1 | ENST00000282841.9 | c.854T>G | p.Val285Gly | missense_variant | 4/4 | 1 | NM_004837.4 | P1 | |
GGPS1 | ENST00000488594.5 | c.854T>G | p.Val285Gly | missense_variant | 4/4 | 1 | P1 | ||
GGPS1 | ENST00000358966.6 | c.854T>G | p.Val285Gly | missense_variant | 4/4 | 2 | P1 | ||
GGPS1 | ENST00000391855.2 | c.692T>G | p.Val231Gly | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;.
Vest4
MutPred
Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);.;
MVP
MPC
0.59
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.