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GeneBe

11-16783795-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001329630.2(PLEKHA7):c.3555C>T(p.Tyr1185=) 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 (★).

Frequency

Genomes: 𝑓 0.0029 ( 13 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 51 hom. )

Consequence

PLEKHA7
NM_001329630.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-16783795-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 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=-1.25 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    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 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLEKHA7NM_001329630.2 linkuse as main transcriptc.3555C>T p.Tyr1185= synonymous_variant 25/27 ENST00000531066.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLEKHA7ENST00000531066.6 linkuse as main transcriptc.3555C>T p.Tyr1185= synonymous_variant 25/275 NM_001329630.2 A1
PLEKHA7ENST00000698836.1 linkuse as main transcriptc.3558C>T p.Tyr1186= synonymous_variant 25/27 P3
PLEKHA7ENST00000637162.1 linkuse as main transcriptc.3189C>T p.Tyr1063= synonymous_variant 21/235
PLEKHA7ENST00000636090.1 linkuse as main transcriptc.1221C>T p.Tyr407= synonymous_variant 9/125

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00289
AC:
440
AN:
152222
Hom.:
13
Cov.:
33
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.:
17
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.:
51
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00286
AC:
435
AN:
152340
Hom.:
13
Cov.:
33
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.:
0
Bravo
AF:
0.00456
Asia WGS
AF:
0.0120
AC:
41
AN:
3478

ClinVar

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

Submissions by phenotype

PLEKHA7-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 23, 2019This 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.

Other links and lift over

dbSNP: rs4757433; hg19: chr11-16805342; API