rs17103541

Positions:

• chr10-122430605-A-G

Variant summary

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

The NM_001001974.4(PLEKHA1):​c.*667A>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 0.093 in 152,394 control chromosomes in the GnomAD database, including 780 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 0.093 (780 hom., cov: 32)
  • Exomes 𝑓: 0.091 (0 hom.)
• Consequence: PLEKHA1 NM_001001974.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA1	NM_001001974.4	c.*667A>G		3_prime_UTR_variant	12/12	ENST00000368990.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.*667A>G		3_prime_UTR_variant	12/12	1	NM_001001974.4	P3
PLEKHA1	ENST00000433307.2	c.*667A>G		3_prime_UTR_variant	11/11	1		P3
PLEKHA1	ENST00000368988.5	c.*1022A>G		3_prime_UTR_variant	12/12	5
PLEKHA1	ENST00000368989.6	c.*771A>G		3_prime_UTR_variant	13/13	5		A1

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14169 AN: 152188 Hom.: 781 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0909 AC: 8 AN: 88 Hom.: 0 Cov.: 0 AF XY: 0.107 AC XY: 6 AN XY: 56

Gnomad4 FIN exome AF: 0.0952

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0930 AC: 14164 AN: 152306 Hom.: 780 Cov.: 32 AF XY: 0.0911 AC XY: 6781 AN XY: 74466

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.0922

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.101

Alfa AF: 0.102 Hom.: 225

Bravo AF: 0.0894

Asia WGS AF: 0.0840 AC: 291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.4
DANN	Benign	0.60

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: rs17103541; hg19: chr10-124190121;