15-90241191-G-C

Variant names:

• chr15-90241191-G-C
• rs758864913
• NM_001013657.3:c.283G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001013657.3(GDPGP1):​c.283G>C​(p.Val95Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V95M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GDPGP1 NM_001013657.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 0 publications found

Genes affected

GDPGP1 (HGNC:34360): (GDP-D-glucose phosphorylase 1) Enables GDP-D-glucose phosphorylase activity. Involved in glucose metabolic process. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284626 (HGNC:):

CIB1 (HGNC:16920): (calcium and integrin binding 1) This gene encodes a member of the EF-hand domain-containing calcium-binding superfamily. The encoded protein interacts with many other proteins, including the platelet integrin alpha-IIb-beta-3, DNA-dependent protein kinase, presenilin-2, focal adhesion kinase, p21 activated kinase, and protein kinase D. The encoded protein may be involved in cell survival and proliferation, and is associated with several disease states including cancer and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

CIB1 Gene-Disease associations (from GenCC):

• epidermodysplasia verruciformis, susceptibility to, 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• epidermodysplasia verruciformis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35602853).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013657.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDPGP1	NM_001013657.3	MANE Select	c.283G>C	p.Val95Leu	missense	Exon 4 of 4	NP_001013679.2	Q6ZNW5
	GDPGP1	NM_001322811.2		c.283G>C	p.Val95Leu	missense	Exon 5 of 5	NP_001309740.1	Q6ZNW5
	CIB1	NR_102428.1		n.104-7488C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDPGP1	ENST00000329600.8	TSL:6 MANE Select	c.283G>C	p.Val95Leu	missense	Exon 4 of 4	ENSP00000368405.3	Q6ZNW5
	GDPGP1	ENST00000559204.6	TSL:1	c.283G>C	p.Val95Leu	missense	Exon 5 of 5	ENSP00000453822.2	Q6ZNW5
	ENSG00000284626	ENST00000641199.1		n.283G>C		non_coding_transcript_exon	Exon 5 of 14	ENSP00000492952.1	A0A286YET3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0068	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.060	T
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.27
MutPred		0.37		Loss of sheet (P = 3e-04)
MVP		0.62
MPC		0.35
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.59
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs758864913; hg19: chr15-90784423;