10-122441338-T-C

Position:

• chr10-122441338-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.*11400T>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 0.859 in 152,030 control chromosomes in the GnomAD database, including 56,192 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 0.86 (56176 hom., cov: 29)
  • Exomes 𝑓: 0.86 (16 hom.)
• Consequence: PLEKHA1 NM_021622.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001377230.1	c.*11400T>C		3_prime_UTR_variant	13/13		NP_001364159.1
PLEKHA1	NM_001377231.1	c.*11400T>C		3_prime_UTR_variant	15/15		NP_001364160.1
PLEKHA1	NM_001377232.1	c.*11400T>C		3_prime_UTR_variant	14/14		NP_001364161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285955	ENST00000650300.1	n.1853-4706A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130398 AN: 151870 Hom.: 56119 Cov.: 29

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.844

GnomAD4 exome AF: 0.857 AC: 36 AN: 42 Hom.: 16 Cov.: 0 AF XY: 0.933 AC XY: 28 AN XY: 30

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.824

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.859 AC: 130512 AN: 151988 Hom.: 56176 Cov.: 29 AF XY: 0.864 AC XY: 64221 AN XY: 74318

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.846

Alfa AF: 0.833 Hom.: 7031

Bravo AF: 0.856

Asia WGS AF: 0.912 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.26

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: rs6585829; hg19: chr10-124200854;