11-16791013-T-G

Variant names:

• chr11-16791013-T-G
• rs761414979
• NM_001329630.2:c.2932A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001329630.2(PLEKHA7):​c.2932A>C​(p.Arg978Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLEKHA7 NM_001329630.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.00007318
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.837
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.837 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.2932A>C	p.Arg978Arg	splice_region synonymous	Exon 20 of 27	NP_001316559.1	E9PKC0
	PLEKHA7	NM_001410960.1		c.2935A>C	p.Arg979Arg	splice_region synonymous	Exon 20 of 27	NP_001397889.1	A0A8V8TMS3
	PLEKHA7	NM_001329631.2		c.2935A>C	p.Arg979Arg	splice_region synonymous	Exon 20 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.2932A>C	p.Arg978Arg	splice_region synonymous	Exon 20 of 27	ENSP00000435389.1	E9PKC0
	PLEKHA7	ENST00000355661.7	TSL:1	c.2932A>C	p.Arg978Arg	splice_region synonymous	Exon 20 of 23	ENSP00000347883.2	Q6IQ23-1
	PLEKHA7	ENST00000530489.5	TSL:1	c.1825A>C	p.Arg609Arg	splice_region synonymous	Exon 11 of 14	ENSP00000433467.1	H0YDE2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461774 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.71
PhyloP100		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000073
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.050		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: rs761414979; hg19: chr11-16812560;