chr1-235342723-T-G

Position:

• chr1-235342723-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• 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]

ACMG classification

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

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
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	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.29	T
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	D
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.

Other links and lift over

hg19: chr1-235506038;