10-122424216-T-G

Variant names:

• chr10-122424216-T-G
• rs4405249
• NM_001001974.4:c.699T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001001974.4(PLEKHA1):​c.699T>G​(p.Arg233Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLEKHA1 NM_001001974.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 31 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA1	NM_001001974.4	MANE Select	c.699T>G	p.Arg233Arg	synonymous	Exon 9 of 12	NP_001001974.1
	PLEKHA1	NM_001377230.1		c.699T>G	p.Arg233Arg	synonymous	Exon 10 of 13	NP_001364159.1
	PLEKHA1	NM_001377231.1		c.699T>G	p.Arg233Arg	synonymous	Exon 12 of 15	NP_001364160.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA1	ENST00000368990.8	TSL:1 MANE Select	c.699T>G	p.Arg233Arg	synonymous	Exon 9 of 12	ENSP00000357986.3
	PLEKHA1	ENST00000392799.7	TSL:1	c.699T>G	p.Arg233Arg	synonymous	Exon 10 of 13	ENSP00000376547.3
	PLEKHA1	ENST00000433307.2	TSL:1	c.699T>G	p.Arg233Arg	synonymous	Exon 8 of 11	ENSP00000394416.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1432446 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 712326

African (AFR) AF: 0.00 AC: 0 AN: 31244

American (AMR) AF: 0.00 AC: 0 AN: 36006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25280

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 79770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103782

Other (OTH) AF: 0.00 AC: 0 AN: 59048

GnomAD4 genome Cov.: 19

Alfa AF: 0.00 Hom.: 105616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.51
PhyloP100		-1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4405249; hg19: chr10-124183732;