16-87604287-C-CCTGCTGCTGCTG

Position:

• chr16-87604287-C-CCTGCTGCTGCTG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001271604.4(JPH3):​c.461_472dupCTGCTGCTGCTG​(p.Ala154_Ala157dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (28 hom., cov: 0)
  • Exomes 𝑓: 0.0084 (103 hom.)
  • Failed GnomAD Quality Control
• 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
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0156 (2348/150050) while in subpopulation AFR AF= 0.0349 (1419/40662). AF 95% confidence interval is 0.0334. There are 28 homozygotes in gnomad4. There are 1128 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2348 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4	c.382+790_382+801dupCTGCTGCTGCTG		intron_variant		ENST00000284262.3	NP_065706.2
JPH3	NM_001271604.4	c.461_472dupCTGCTGCTGCTG	p.Ala154_Ala157dup	disruptive_inframe_insertion	2/2		NP_001258533.1
JPH3	NM_001271605.3	c.*159_*170dupCTGCTGCTGCTG		3_prime_UTR_variant	2/2		NP_001258534.1
JPH3	NR_073379.3	n.96+2388_96+2399dupCTGCTGCTGCTG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3	c.382+790_382+801dupCTGCTGCTGCTG		intron_variant		1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000301008.5	n.721_732dupCTGCTGCTGCTG		non_coding_transcript_exon_variant	2/2	1
JPH3	ENST00000537256.5	n.96+2388_96+2399dupCTGCTGCTGCTG		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2346 AN: 149942 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00972

Gnomad ASJ AF: 0.00638

Gnomad EAS AF: 0.00630

Gnomad SAS AF: 0.00170

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00870

Gnomad OTH AF: 0.0127

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00840 AC: 10772 AN: 1282142 Hom.: 103 Cov.: 30 AF XY: 0.00824 AC XY: 5212 AN XY: 632666

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.00853

Gnomad4 ASJ exome AF: 0.00467

Gnomad4 EAS exome AF: 0.00736

Gnomad4 SAS exome AF: 0.00374

Gnomad4 FIN exome AF: 0.00939

Gnomad4 NFE exome AF: 0.00785

Gnomad4 OTH exome AF: 0.00984

GnomAD4 genome AF: 0.0156 AC: 2348 AN: 150050 Hom.: 28 Cov.: 0 AF XY: 0.0154 AC XY: 1128 AN XY: 73212

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.00970

Gnomad4 ASJ AF: 0.00638

Gnomad4 EAS AF: 0.00632

Gnomad4 SAS AF: 0.00170

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.00870

Gnomad4 OTH AF: 0.0125

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;