NM_001329630.2:c.3335C>G

Variant names:

• chr11-16789118-G-C
• rs576126330
• NM_001329630.2:c.3335C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001329630.2(PLEKHA7):​c.3335C>G​(p.Pro1112Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000619 in 1,453,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PLEKHA7 NM_001329630.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.51

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30157495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.3335C>G	p.Pro1112Arg	missense_variant	Exon 23 of 27	ENST00000531066.6	NP_001316559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.3335C>G	p.Pro1112Arg	missense_variant	Exon 23 of 27	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1453558 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 723510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.0	.;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Benign	0.13
Sift	Benign	0.071	T;D;.
Sift4G	Uncertain	0.016	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.63
MutPred		0.36		Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);.;
MVP		0.52
MPC		0.61
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.15
gMVP		0.24

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: rs576126330; hg19: chr11-16810665; COSMIC: COSV100261952; COSMIC: COSV100261952;