16-87604287-C-CCTGCTG

Position:

• chr16-87604287-C-CCTGCTG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BA1

The NM_001271604.4(JPH3):​c.467_472dupCTGCTG​(p.Ala156_Ala157dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,424,918 control chromosomes in the GnomAD database, including 23,841 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5340 hom., cov: 0)
  • Exomes 𝑓: 0.27 (18501 hom.)
• Consequence: JPH3 NM_001271604.4 disruptive_inframe_insertion
• 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 -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001271604.4
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4	c.382+796_382+801dupCTGCTG		intron_variant		ENST00000284262.3	NP_065706.2
JPH3	NM_001271604.4	c.467_472dupCTGCTG	p.Ala156_Ala157dup	disruptive_inframe_insertion	2/2		NP_001258533.1
JPH3	NM_001271605.3	c.*165_*170dupCTGCTG		3_prime_UTR_variant	2/2		NP_001258534.1
JPH3	NR_073379.3	n.96+2394_96+2399dupCTGCTG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3	c.382+796_382+801dupCTGCTG		intron_variant		1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000301008.5	n.727_732dupCTGCTG		non_coding_transcript_exon_variant	2/2	1
JPH3	ENST00000537256.5	n.96+2394_96+2399dupCTGCTG		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 38590 AN: 149850 Hom.: 5341 Cov.: 0

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.270 AC: 344416 AN: 1274960 Hom.: 18501 Cov.: 30 AF XY: 0.272 AC XY: 171239 AN XY: 629186

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.257 AC: 38600 AN: 149958 Hom.: 5340 Cov.: 0 AF XY: 0.258 AC XY: 18882 AN XY: 73160

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.0925

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;