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GeneBe

11-16783720-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001329630.2(PLEKHA7):c.3630C>T(p.Arg1210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,478,732 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

PLEKHA7
NM_001329630.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0530
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-16783720-G-A is Benign according to our data. Variant chr11-16783720-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3047626.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.053 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLEKHA7NM_001329630.2 linkuse as main transcriptc.3630C>T p.Arg1210= synonymous_variant 25/27 ENST00000531066.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLEKHA7ENST00000531066.6 linkuse as main transcriptc.3630C>T p.Arg1210= synonymous_variant 25/275 NM_001329630.2 A1
PLEKHA7ENST00000698836.1 linkuse as main transcriptc.3633C>T p.Arg1211= synonymous_variant 25/27 P3
PLEKHA7ENST00000637162.1 linkuse as main transcriptc.3264C>T p.Arg1088= synonymous_variant 21/235
PLEKHA7ENST00000636090.1 linkuse as main transcriptc.1296C>T p.Arg432= synonymous_variant 9/125

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000630
AC:
96
AN:
152268
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000964
Gnomad AMI
AF:
0.0439
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000363
AC:
32
AN:
88160
Hom.:
0
AF XY:
0.000372
AC XY:
18
AN XY:
48362
show subpopulations
Gnomad AFR exome
AF:
0.000784
Gnomad AMR exome
AF:
0.000314
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000690
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000621
Gnomad OTH exome
AF:
0.000373
GnomAD4 exome
AF:
0.000563
AC:
747
AN:
1326464
Hom.:
0
Cov.:
31
AF XY:
0.000541
AC XY:
353
AN XY:
652186
show subpopulations
Gnomad4 AFR exome
AF:
0.000208
Gnomad4 AMR exome
AF:
0.000360
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000569
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000667
Gnomad4 OTH exome
AF:
0.000450
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000630
AC:
96
AN:
152268
Hom.:
2
Cov.:
33
AF XY:
0.000672
AC XY:
50
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0000964
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000470
Hom.:
0
Bravo
AF:
0.000774

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PLEKHA7-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 24, 2020This variant is classified as likely 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
-0.25
Cadd
Benign
7.3
Dann
Benign
0.76

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.

Other links and lift over

dbSNP: rs61745332; hg19: chr11-16805267; API