5-140378-CC-AT

Variant names:

• chr5-140378-CC-AT
• NM_052909.5:c.1139_1140delCCinsAT
• PLEKHG4B p.Ser380Tyr

Variant summary

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

The NM_052909.5(PLEKHG4B):​c.1139_1140delCCinsAT​(p.Ser380Tyr) 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. S380C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHG4B NM_052909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 0 publications found

Genes affected

PLEKHG4B (HGNC:29399): (pleckstrin homology and RhoGEF domain containing G4B) This gene encodes a large protein that contains a pleckstrin homology domain and may function as a guanine nucleotide exchange factor. [provided by RefSeq, May 2017]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052909.5. 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
	PLEKHG4B	NM_052909.5	MANE Select	c.1139_1140delCCinsAT	p.Ser380Tyr	missense	N/A	NP_443141.4	Q96PX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG4B	ENST00000637938.2	TSL:5 MANE Select	c.1139_1140delCCinsAT	p.Ser380Tyr	missense	N/A	ENSP00000490806.1	Q96PX9
	PLEKHG4B	ENST00000283426.11	TSL:1	c.71_72delCCinsAT	p.Ser24Tyr	missense	N/A	ENSP00000283426.6	A0AAK2PKJ8
	PLEKHG4B	ENST00000924300.1		c.1139_1140delCCinsAT	p.Ser380Tyr	missense	N/A	ENSP00000594359.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33

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: chr5-140493;