chr16-87604287-CCTGCTG-C

Position:

• chr16-87604287-CCTGCTG-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_020655.4(JPH3):​c.382+796_382+801del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,432,648 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (9 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (3 hom.)
• 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 Benign. Variant got -9 ACMG points.

• BP6: Variant 16-87604287-CCTGCTG-C is Benign according to our data. Variant chr16-87604287-CCTGCTG-C is described in Lovd as [Benign]. Variant chr16-87604287-CCTGCTG-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00672 (1008/150060) while in subpopulation AFR AF= 0.0219 (890/40662). AF 95% confidence interval is 0.0207. There are 9 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1008 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH3	NM_020655.4	c.382+796_382+801del		intron_variant		ENST00000284262.3
JPH3	NM_001271604.4	c.467_472del	p.Ala156_Ala157del	inframe_deletion	2/2
JPH3	NM_001271605.3	c.*165_*170del		3_prime_UTR_variant	2/2
JPH3	NR_073379.3	n.96+2394_96+2399del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH3	ENST00000284262.3	c.382+796_382+801del		intron_variant		1	NM_020655.4	P1
JPH3	ENST00000301008.5	n.727_732del		non_coding_transcript_exon_variant	2/2	1
JPH3	ENST00000537256.5	n.96+2394_96+2399del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 1002 AN: 149952 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00889

Gnomad AMR AF: 0.00258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000591

Gnomad SAS AF: 0.00276

Gnomad FIN AF: 0.0000971

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000593

Gnomad OTH AF: 0.00633

GnomAD4 exome AF: 0.00104 AC: 1339 AN: 1282588 Hom.: 3 AF XY: 0.00102 AC XY: 644 AN XY: 632894

Gnomad4 AFR exome AF: 0.0178

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.0000462

Gnomad4 EAS exome AF: 0.000166

Gnomad4 SAS exome AF: 0.00220

Gnomad4 FIN exome AF: 0.000136

Gnomad4 NFE exome AF: 0.000495

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00672 AC: 1008 AN: 150060 Hom.: 9 Cov.: 0 AF XY: 0.00649 AC XY: 475 AN XY: 73218

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.00257

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000593

Gnomad4 SAS AF: 0.00255

Gnomad4 FIN AF: 0.0000971

Gnomad4 NFE AF: 0.000593

Gnomad4 OTH AF: 0.00723

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;