10-122424214-CGT-AGA

Variant names:

• chr10-122424214-CGT-AGA
• NM_001001974.4:c.697_699delCGTinsAGA
• PLEKHA1 p.234

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001001974.4(PLEKHA1):​c.697_699delCGTinsAGA​(p.234) variant causes a synonymous change involving the alteration of a conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. R233R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 19)
• Consequence: PLEKHA1 NM_001001974.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.19
• Publications: 0 publications found

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001974.4. 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
	PLEKHA1	NM_001001974.4	MANE Select	c.697_699delCGTinsAGA	p.234	synonymous	N/A	NP_001001974.1	Q9HB21-1
	PLEKHA1	NM_001377230.1		c.697_699delCGTinsAGA	p.234	synonymous	N/A	NP_001364159.1	Q9HB21-1
	PLEKHA1	NM_001377231.1		c.697_699delCGTinsAGA	p.234	synonymous	N/A	NP_001364160.1	Q9HB21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA1	ENST00000368990.8	TSL:1 MANE Select	c.697_699delCGTinsAGA	p.234	synonymous	N/A	ENSP00000357986.3	Q9HB21-1
	PLEKHA1	ENST00000392799.7	TSL:1	c.697_699delCGTinsAGA	p.234	synonymous	N/A	ENSP00000376547.3	Q9HB21-1
	PLEKHA1	ENST00000433307.2	TSL:1	c.697_699delCGTinsAGA	p.234	synonymous	N/A	ENSP00000394416.1	Q9HB21-1

Frequencies

GnomAD3 genomes Cov.: 19

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

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.2

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: chr10-124183730;