19-55014999-GGG-TGC

Variant names:

• chr19-55014999-GGG-TGC
• NM_016363.5:c.940_942delCCCinsGCA
• GP6 p.Pro314Ala

Variant summary

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

The NM_016363.5(GP6):​c.940_942delCCCinsGCA​(p.Pro314Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. P314H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GP6 NM_016363.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

GP6 (HGNC:14388): (glycoprotein VI platelet) This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016363.5. 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
	GP6	NM_016363.5	MANE Select	c.940_942delCCCinsGCA	p.Pro314Ala	missense	N/A	NP_057447.5	Q9HCN6-1
	GP6	NM_001083899.2		c.944_946delCCCinsGCA	p.AlaPro315GlyThr	missense	N/A	NP_001077368.2	Q9HCN6-3
	GP6	NM_001256017.2		c.886_888delCCCinsGCA	p.Pro296Ala	missense	N/A	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.940_942delCCCinsGCA	p.Pro314Ala	missense	N/A	ENSP00000394922.1	Q9HCN6-1
	GP6	ENST00000310373.7	TSL:1	c.944_946delCCCinsGCA	p.AlaPro315GlyThr	missense	N/A	ENSP00000308782.3	Q9HCN6-3
	GP6	ENST00000333884.2	TSL:1	c.886_888delCCCinsGCA	p.Pro296Ala	missense	N/A	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-55526367;