16-87604287-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr16-87604287-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020655.4(JPH3):​c.382+772_382+801dup variant causes a intron 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 0.00059 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00018 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: JPH3 NM_020655.4 intron
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH3	NM_020655.4	c.382+772_382+801dup		intron_variant		ENST00000284262.3
JPH3	NM_001271604.4	c.443_472dup	p.Ala148_Ala157dup	inframe_insertion	2/2
JPH3	NM_001271605.3	c.*141_*170dup		3_prime_UTR_variant	2/2
JPH3	NR_073379.3	n.96+2370_96+2399dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH3	ENST00000284262.3	c.382+772_382+801dup		intron_variant		1	NM_020655.4	P1
JPH3	ENST00000301008.5	n.703_732dup		non_coding_transcript_exon_variant	2/2	1
JPH3	ENST00000537256.5	n.96+2370_96+2399dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000580 AC: 87 AN: 149958 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000595

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.000534

Gnomad OTH AF: 0.000974

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000179 AC: 229 AN: 1282836 Hom.: 7 Cov.: 30 AF XY: 0.000166 AC XY: 105 AN XY: 633000

Gnomad4 AFR exome AF: 0.000600

Gnomad4 AMR exome AF: 0.000741

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000125

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.000102

Gnomad4 NFE exome AF: 0.000133

Gnomad4 OTH exome AF: 0.000431

GnomAD4 genome AF: 0.000586 AC: 88 AN: 150066 Hom.: 1 Cov.: 0 AF XY: 0.000601 AC XY: 44 AN XY: 73222

Gnomad4 AFR AF: 0.000787

Gnomad4 AMR AF: 0.000594

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000425

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000534

Gnomad4 OTH AF: 0.000963

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;