rs193920946

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA4	NM_020904.3	c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 20	ENST00000263265.11	NP_065955.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA4	ENST00000263265.11	c.20_28delGCAGCAGCC	p.Arg7_Ser9del	disruptive_inframe_deletion	Exon 2 of 20	1	NM_020904.3	ENSP00000263265.5

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920946; hg19: chr19-49370849;