16-87604287-CCTG-C

Position:

• chr16-87604287-CCTG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3 BP6 BA1

The NM_001271604.4(JPH3):​c.470_472delCTG​(p.Ala157del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,389,866 control chromosomes in the GnomAD database, including 293 homozygotes. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.033 (232 hom., cov: 0)
  • Exomes 𝑓: 0.0074 (61 hom.)
• Consequence: JPH3 NM_001271604.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

Genes affected

JPH3 (HGNC:14203): (junctophilin 3) Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. CAG/CTG repeat expansion from normally 6-28 repeats to 40-59 repeats in the 3' UTR of this gene have been associated with Huntington disease-like 2 (HDL2). This gene is a member of the junctophilin gene family. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2016]

JPH3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001271604.4
• BP6: Variant 16-87604287-CCTG-C is Benign according to our data. Variant chr16-87604287-CCTG-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4	c.382+799_382+801delCTG		intron_variant		ENST00000284262.3	NP_065706.2
JPH3	NM_001271604.4	c.470_472delCTG	p.Ala157del	disruptive_inframe_deletion	2/2		NP_001258533.1
JPH3	NM_001271605.3	c.*168_*170delCTG		3_prime_UTR_variant	2/2		NP_001258534.1
JPH3	NR_073379.3	n.96+2397_96+2399delCTG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3	c.382+799_382+801delCTG		intron_variant		1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000301008.5	n.730_732delCTG		non_coding_transcript_exon_variant	2/2	1
JPH3	ENST00000537256.5	n.96+2397_96+2399delCTG		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4883 AN: 149892 Hom.: 231 Cov.: 0

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0145

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.00912

Gnomad FIN AF: 0.00165

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00264

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00738 AC: 9148 AN: 1239868 Hom.: 61 AF XY: 0.00723 AC XY: 4404 AN XY: 609046

Gnomad4 AFR exome AF: 0.0918

Gnomad4 AMR exome AF: 0.0175

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.0241

Gnomad4 SAS exome AF: 0.0108

Gnomad4 FIN exome AF: 0.00420

Gnomad4 NFE exome AF: 0.00383

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0327 AC: 4898 AN: 149998 Hom.: 232 Cov.: 0 AF XY: 0.0321 AC XY: 2346 AN XY: 73192

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0145

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.00165

Gnomad4 NFE AF: 0.00264

Gnomad4 OTH AF: 0.0284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs71156237; hg19: chr16-87637893;