5-57246387-C-T

Variant names:

• chr5-57246387-C-T
• rs1426368612
• NM_022913.4:c.566C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022913.4(GPBP1):​c.566C>T​(p.Pro189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPBP1 NM_022913.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99
• Publications: 0 publications found

Genes affected

GPBP1 (HGNC:29520): (GC-rich promoter binding protein 1) This gene was originally isolated by subtractive hybridization of cDNAs expressed in atherosclerotic plaques with a thrombus, and was found to be expressed only in vascular smooth muscle cells. However, a shorter splice variant was found to be more ubiquitously expressed. This protein is suggested to play a role in the development of atherosclerosis. Studies in mice suggest that it may also function as a GC-rich promoter-specific trans-activating transcription factor. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022913.4. 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
	GPBP1	NM_022913.4	MANE Select	c.566C>T	p.Pro189Leu	missense	Exon 7 of 12	NP_075064.1	Q86WP2-1
	GPBP1	NM_001331037.2		c.626C>T	p.Pro209Leu	missense	Exon 8 of 13	NP_001317966.1	D4PHA4
	GPBP1	NM_001127236.2		c.587C>T	p.Pro196Leu	missense	Exon 6 of 11	NP_001120708.1	Q86WP2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBP1	ENST00000506184.7	TSL:1 MANE Select	c.566C>T	p.Pro189Leu	missense	Exon 7 of 12	ENSP00000421202.2	Q86WP2-1
	GPBP1	ENST00000264779.6	TSL:1	c.587C>T	p.Pro196Leu	missense	Exon 6 of 11	ENSP00000264779.6	Q86WP2-2
	GPBP1	ENST00000514387.6	TSL:1	c.53C>T	p.Pro18Leu	missense	Exon 6 of 11	ENSP00000421709.2	Q86WP2-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.012
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.15
Sift	Uncertain	0.012	D
Sift4G	Benign	0.082	T
Polyphen		0.57	P
Vest4		0.75
MutPred		0.48		Loss of disorder (P = 0.0294)
MVP		0.082
MPC		0.36
ClinPred		0.94	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.53
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1426368612; hg19: chr5-56542214; COSMIC: COSV104587457; COSMIC: COSV104587457;