NM_001329630.2:c.3189A>G

Variant names:

• chr11-16789264-T-C
• rs149883568
• NM_001329630.2:c.3189A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_001329630.2(PLEKHA7):​c.3189A>G​(p.Ser1063Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,628 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. Synonymous variant affecting the same amino acid position (i.e. S1063S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: PLEKHA7 NM_001329630.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12820414).
• BP7: Synonymous conserved (PhyloP=0.222 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA7	NM_001329630.2	MANE Select	c.3189A>G	p.Ser1063Ser	synonymous	Exon 23 of 27	NP_001316559.1	E9PKC0
	PLEKHA7	NM_001410960.1		c.3192A>G	p.Ser1064Ser	synonymous	Exon 23 of 27	NP_001397889.1	A0A8V8TMS3
	PLEKHA7	NM_001329631.2		c.3192A>G	p.Ser1064Ser	synonymous	Exon 23 of 23	NP_001316560.1	Q6IQ23-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA7	ENST00000531066.6	TSL:5 MANE Select	c.3189A>G	p.Ser1063Ser	synonymous	Exon 23 of 27	ENSP00000435389.1	E9PKC0
	PLEKHA7	ENST00000355661.7	TSL:1	c.3189A>G	p.Ser1063Ser	synonymous	Exon 23 of 23	ENSP00000347883.2	Q6IQ23-1
	PLEKHA7	ENST00000530489.5	TSL:1	c.2082A>G	p.Ser694Ser	synonymous	Exon 14 of 14	ENSP00000433467.1	H0YDE2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000402 AC: 10 AN: 248628 AF XY: 0.0000668

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1461344 Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 727004

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152284 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.4
DANN	Benign	0.76
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.22
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.20
Vest4		0.19
MVP		0.32
ClinPred		0.16	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs149883568; hg19: chr11-16810811;