10-122432914-T-C

Position:

• chr10-122432914-T-C

Variant summary

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

The NM_021622.5(PLEKHA1):​c.*2976T>C 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 152,104 control chromosomes in the GnomAD database, including 24,466 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 (24466 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PLEKHA1 NM_021622.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001377230.1	c.*2976T>C		3_prime_UTR_variant	13/13		NP_001364159.1
PLEKHA1	NM_001377231.1	c.*2976T>C		3_prime_UTR_variant	15/15		NP_001364160.1
PLEKHA1	NM_001377232.1	c.*2976T>C		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: 85065 AN: 151982 Hom.: 24434 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.560 AC: 85152 AN: 152100 Hom.: 24466 Cov.: 33 AF XY: 0.569 AC XY: 42273 AN XY: 74334

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.528

Alfa AF: 0.567 Hom.: 4785

Bravo AF: 0.565

Asia WGS AF: 0.585 AC: 2031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.65

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: rs10510110; hg19: chr10-124192430;