2-158533301-A-T

Variant names:

• chr2-158533301-A-T
• NM_003628.6:c.117A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_003628.6(PKP4):​c.117A>T​(p.Ala39Ala) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKP4 NM_003628.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.139
• Publications: 0 publications found

Genes affected

PKP4 (HGNC:9026): (plakophilin 4) Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-158533301-A-T is Benign according to our data. Variant chr2-158533301-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3419605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.139 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003628.6. 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
	PKP4	NM_003628.6	MANE Select	c.117A>T	p.Ala39Ala	synonymous	Exon 2 of 22	NP_003619.2	Q99569-1
	PKP4	NM_001377218.1		c.117A>T	p.Ala39Ala	synonymous	Exon 2 of 22	NP_001364147.1	Q99569-1
	PKP4	NM_001304969.3		c.117A>T	p.Ala39Ala	synonymous	Exon 2 of 22	NP_001291898.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP4	ENST00000389759.8	TSL:1 MANE Select	c.117A>T	p.Ala39Ala	synonymous	Exon 2 of 22	ENSP00000374409.3	Q99569-1
	PKP4	ENST00000389757.7	TSL:1	c.117A>T	p.Ala39Ala	synonymous	Exon 2 of 21	ENSP00000374407.3	Q99569-2
	PKP4	ENST00000426248.7	TSL:1	n.117A>T		non_coding_transcript_exon	Exon 2 of 22	ENSP00000396827.2	E7EST6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.6
DANN	Benign	0.71
PhyloP100		0.14
PromoterAI		0.023	Neutral
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

hg19: chr2-159389813;