Genetic Variant NM_001329630.2:c.3555C>T (chr11-16783795-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001329630.2(PLEKHA7):c.3555C>T(p.Tyr1185Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,512,736 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 51 hom. )

Consequence

PLEKHA7
NM_001329630.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.25

Variant links:

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 11-16783795-G-A is Benign according to our data. Variant chr11-16783795-G-A is described in ClinVar as [Benign]. Clinvar id is 3044870.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00286 (435/152340) while in subpopulation EAS AF= 0.0388 (201/5174). AF 95% confidence interval is 0.0345. There are 13 homozygotes in gnomad4. There are 225 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2 link	c.3555C>T	p.Tyr1185Tyr	synonymous_variant	Exon 25 of 27	ENST00000531066.6	NP_001316559.1	Q6IQ23E9PKC0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLEKHA7	ENST00000531066.6 link	c.3555C>T	p.Tyr1185Tyr	synonymous_variant	Exon 25 of 27	5	NM_001329630.2	ENSP00000435389.1	E9PKC0
PLEKHA7	ENST00000698836.1 link	c.3558C>T	p.Tyr1186Tyr	synonymous_variant	Exon 25 of 27			ENSP00000513972.1	A0A8V8TMS3
PLEKHA7	ENST00000637162.1 link	c.3186C>T	p.Tyr1062Tyr	synonymous_variant	Exon 21 of 23	5		ENSP00000489780.1	A0A1B0GTN9
PLEKHA7	ENST00000636090.1 link	c.1218C>T	p.Tyr406Tyr	synonymous_variant	Exon 9 of 12	5		ENSP00000490167.1	A0A1B0GUM1

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0390

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00735

AC:

841

AN:

114362

Hom.:

AF XY:

0.00590

AC XY:

370

AN XY:

62678

show subpopulations

Gnomad AFR exome

AF:

0.000601

Gnomad AMR exome

AF:

0.0282

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0309

Gnomad SAS exome

AF:

0.000570

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.00374

GnomAD4 exome

AF:

0.00174

AC:

2370

AN:

1360396

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1098

AN XY:

670662

show subpopulations

Gnomad4 AFR exome

AF:

0.000231

Gnomad4 AMR exome

AF:

0.0251

Gnomad4 ASJ exome

AF:

0.0000407

Gnomad4 EAS exome

AF:

0.0397

Gnomad4 SAS exome

AF:

0.000634

Gnomad4 FIN exome

AF:

0.000149

Gnomad4 NFE exome

AF:

0.0000590

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00286

AC:

435

AN:

152340

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0388

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00456

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLEKHA7-related disorder

Benign:1

Apr 23, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.024

DANN

Benign

0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over