16-4885145-C-G

Position:

• chr16-4885145-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000345988.7(PPL):​c.3510G>C​(p.Val1170=) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PPL ENST00000345988.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

Genes affected

PPL (HGNC:9273): (periplakin) The protein encoded by this gene is a component of desmosomes and of the epidermal cornified envelope in keratinocytes. The N-terminal domain of this protein interacts with the plasma membrane and its C-terminus interacts with intermediate filaments. Through its rod domain, this protein forms complexes with envoplakin. This protein may serve as a link between the cornified envelope and desmosomes as well as intermediate filaments. AKT1/PKB, a protein kinase mediating a variety of cell growth and survival signaling processes, is reported to interact with this protein, suggesting a possible role for this protein as a localization signal in AKT1-mediated signaling. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.246 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPL	NM_002705.5	c.3510G>C	p.Val1170=	synonymous_variant	22/22	ENST00000345988.7	NP_002696.4
PPL	XM_017023374.3	c.3597G>C	p.Val1199=	synonymous_variant	22/22		XP_016878863.1
PPL	XM_017023375.3	c.3558G>C	p.Val1186=	synonymous_variant	22/22		XP_016878864.1
PPL	XM_006720902.5	c.3549G>C	p.Val1183=	synonymous_variant	22/22		XP_006720965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPL	ENST00000345988.7	c.3510G>C	p.Val1170=	synonymous_variant	22/22	1	NM_002705.5	ENSP00000340510	P3
PPL	ENST00000590782.6	c.3504G>C	p.Val1168=	synonymous_variant	22/22	5		ENSP00000465640	A1
PPL	ENST00000592772.1	c.1773G>C	p.Val591=	synonymous_variant	10/10	5		ENSP00000467699

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 85

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.5
DANN	Benign	0.80

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: rs1049206; hg19: chr16-4935146;