chr19-48867592-AGGCTGCTGC-A

Variant names:

• chr19-48867592-AGGCTGCTGC-A
• rs193920946
• NM_020904.3:c.20_28delGCAGCAGCC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_020904.3(PLEKHA4):​c.20_28delGCAGCAGCC​(p.Arg7_Ser9del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHA4 NM_020904.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.88
• Publications: 0 publications found

Genes affected

PLEKHA4 (HGNC:14339): (pleckstrin homology domain containing A4) This gene encodes a pleckstrin homology (PH) domain-containing protein. The PH domain is found near the N-terminus and contains a putative phosphatidylinositol 3, 4, 5-triphosphate-binding motif (PPBM). Elevated expression of this gene has been observed in some melanomas. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_020904.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020904.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA4	NM_020904.3	MANE Select	c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 20	NP_065955.2
	PLEKHA4	NM_001438306.1		c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 20	NP_001425235.1
	PLEKHA4	NM_001438307.1		c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 19	NP_001425236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA4	ENST00000263265.11	TSL:1 MANE Select	c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 20	ENSP00000263265.5
	PLEKHA4	ENST00000355496.9	TSL:1	c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 17	ENSP00000347683.4
	PLEKHA4	ENST00000594100.2	TSL:3	c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 19	ENSP00000471274.2

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

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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

Other links and lift over

dbSNP: rs193920946; hg19: chr19-49370849;