10-122424216-T-C

Position:

• chr10-122424216-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001001974.4(PLEKHA1):​c.699T>C​(p.Arg233Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,575,738 control chromosomes in the GnomAD database, including 580,811 homozygotes. 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: 𝑓 0.88 (56648 hom., cov: 19)
  • Exomes 𝑓: 0.85 (524163 hom.)
• Consequence: PLEKHA1 NM_001001974.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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]

PLEKHA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.699T>C	p.Arg233Arg	synonymous_variant	9/12	ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.699T>C	p.Arg233Arg	synonymous_variant	9/12	1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.885 AC: 127162 AN: 143756 Hom.: 56600 Cov.: 19

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.869

GnomAD3 exomes AF: 0.882 AC: 195327 AN: 221372 Hom.: 86646 AF XY: 0.880 AC XY: 106081 AN XY: 120484

Gnomad AFR exome AF: 0.969

Gnomad AMR exome AF: 0.913

Gnomad ASJ exome AF: 0.866

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.952

Gnomad FIN exome AF: 0.842

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.865

GnomAD4 exome AF: 0.854 AC: 1223521 AN: 1431898 Hom.: 524163 Cov.: 42 AF XY: 0.857 AC XY: 610162 AN XY: 712068

Gnomad4 AFR exome AF: 0.971

Gnomad4 AMR exome AF: 0.909

Gnomad4 ASJ exome AF: 0.865

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.953

Gnomad4 FIN exome AF: 0.843

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.870

GnomAD4 genome AF: 0.885 AC: 127253 AN: 143840 Hom.: 56648 Cov.: 19 AF XY: 0.887 AC XY: 61523 AN XY: 69326

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.871

Alfa AF: 0.851 Hom.: 88373

Bravo AF: 0.895

Asia WGS AF: 0.980 AC: 3405 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4405249; hg19: chr10-124183732;