10-122433665-T-G

Position:

• chr10-122433665-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021622.5(PLEKHA1):​c.*3727T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,962 control chromosomes in the GnomAD database, including 24,424 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 0.56 (24424 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PLEKHA1 NM_021622.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001377230.1	c.*3727T>G		3_prime_UTR_variant	13/13		NP_001364159.1
PLEKHA1	NM_001377231.1	c.*3727T>G		3_prime_UTR_variant	15/15		NP_001364160.1
PLEKHA1	NM_001377232.1	c.*3727T>G		3_prime_UTR_variant	14/14		NP_001364161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84969 AN: 151840 Hom.: 24393 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.560 AC: 85056 AN: 151958 Hom.: 24424 Cov.: 32 AF XY: 0.568 AC XY: 42204 AN XY: 74248

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.528

Alfa AF: 0.499 Hom.: 26496

Bravo AF: 0.565

Asia WGS AF: 0.589 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.40

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: rs2280141; hg19: chr10-124193181;