chr10-122435525-G-C

Position:

• chr10-122435525-G-C

Variant summary

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

The NM_021622.5(PLEKHA1):​c.*5587G>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 0.14 in 152,150 control chromosomes in the GnomAD database, including 1,626 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 0.14 (1626 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: PLEKHA1 NM_021622.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

PLEKHA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001195608.2	c.*5942G>C		3_prime_UTR_variant	14/14		NP_001182537.1
PLEKHA1	NM_001330178.2	c.*5691G>C		3_prime_UTR_variant	14/14		NP_001317107.1
PLEKHA1	NM_001377230.1	c.*5587G>C		3_prime_UTR_variant	13/13		NP_001364159.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21235 AN: 152032 Hom.: 1625 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.138

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.140 AC: 21260 AN: 152150 Hom.: 1626 Cov.: 31 AF XY: 0.137 AC XY: 10193 AN XY: 74400

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.137

Alfa AF: 0.118 Hom.: 167

Bravo AF: 0.143

Asia WGS AF: 0.181 AC: 627 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
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: rs4752695; hg19: chr10-124195041;