11-16791062-G-T

Variant names:

• chr11-16791062-G-T
• rs756351573
• NM_001329630.2:c.2883C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001329630.2(PLEKHA7):​c.2883C>A​(p.Asp961Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHA7 NM_001329630.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19940892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.2883C>A	p.Asp961Glu	missense_variant	Exon 20 of 27	ENST00000531066.6	NP_001316559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.2883C>A	p.Asp961Glu	missense_variant	Exon 20 of 27	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	1.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.37	N
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.27
Sift	Benign	0.31	T;T;.
Sift4G	Uncertain	0.040	D;T;.
Polyphen		1.0	D;D;.
Vest4		0.66
MutPred		0.18		Gain of methylation at K964 (P = 0.0911);Gain of methylation at K964 (P = 0.0911);.;
MVP		0.36
MPC		0.72
ClinPred		0.98	D
GERP RS		-3.5
Varity_R		0.14
gMVP		0.19

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: rs756351573; hg19: chr11-16812609;