10-122424194-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001001974.4(PLEKHA1):c.682-5G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLEKHA1 NM_001001974.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003156
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.667

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 10-122424194-G-T is Benign according to our data. Variant chr10-122424194-G-T is described in ClinVar as [Benign]. Clinvar id is 779937.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA1	NM_001001974.4	c.682-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000368990.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.682-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001001974.4	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3369 AN: 31932 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.109

GnomAD3 exomes AF: 0.0233 AC: 878 AN: 37750 Hom.: 0 AF XY: 0.0225 AC XY: 446 AN XY: 19800

Gnomad AFR exome AF: 0.00636

Gnomad AMR exome AF: 0.0314

Gnomad ASJ exome AF: 0.0179

Gnomad EAS exome AF: 0.0239

Gnomad SAS exome AF: 0.0226

Gnomad FIN exome AF: 0.0966

Gnomad NFE exome AF: 0.0142

Gnomad OTH exome AF: 0.0238

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00298 AC: 3007 AN: 1009500 Hom.: 0 Cov.: 30 AF XY: 0.00298 AC XY: 1481 AN XY: 497574

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.00387

Gnomad4 EAS exome AF: 0.00282

Gnomad4 SAS exome AF: 0.00500

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.00229

Gnomad4 OTH exome AF: 0.00214

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.106 AC: 3370 AN: 31942 Hom.: 0 Cov.: 0 AF XY: 0.0940 AC XY: 1506 AN XY: 16018

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.0862

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.0395

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.109

Alfa AF: 0.00247 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	5.5
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00032
dbscSNV1_RF	Benign	0.0080
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: rs774089419; hg19: chr10-124183710; COSMIC: COSV64570666;