1-201284153-A-G

Position:

• chr1-201284153-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001005337.3(PKP1):​c.202+249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,304 control chromosomes in the GnomAD database, including 66,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.94 (66811 hom., cov: 33)
• Consequence: PKP1 NM_001005337.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

Genes affected

PKP1 (HGNC:9023): (plakophilin 1) This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This protein may be involved in molecular recruitment and stabilization during desmosome formation. Mutations in this gene have been associated with the ectodermal dysplasia/skin fragility syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-201284153-A-G is Benign according to our data. Variant chr1-201284153-A-G is described in ClinVar as [Benign]. Clinvar id is 1272211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP1	NM_001005337.3	c.202+249A>G		intron_variant		ENST00000367324.8	NP_001005337.1
PKP1	NM_000299.4	c.202+249A>G		intron_variant			NP_000290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP1	ENST00000367324.8	c.202+249A>G		intron_variant		1	NM_001005337.3	ENSP00000356293	P1
PKP1	ENST00000263946.7	c.202+249A>G		intron_variant		5		ENSP00000263946
PKP1	ENST00000352845.3	c.202+249A>G		intron_variant		5		ENSP00000295597

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142487 AN: 152186 Hom.: 66764 Cov.: 33

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.939

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.936 AC: 142591 AN: 152304 Hom.: 66811 Cov.: 33 AF XY: 0.935 AC XY: 69643 AN XY: 74470

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.924

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.939

Alfa AF: 0.950 Hom.: 3356

Bravo AF: 0.937

Asia WGS AF: 0.972 AC: 3380 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.67

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: rs854715; hg19: chr1-201253281;