NM_020655.4:c.382+787_382+801dupCTGCTGCTGCTGCTG

Variant names:

• chr16-87604287-C-CCTGCTGCTGCTGCTG
• rs71156237
• NM_020655.4:c.382+787_382+801dupCTGCTGCTGCTGCTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_020655.4(JPH3):​c.382+787_382+801dupCTGCTGCTGCTGCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (61 hom.)
  • Failed GnomAD Quality Control
• Consequence: JPH3 NM_020655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Huntington disease-like 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1861/150056) while in subpopulation AFR AF = 0.0412 (1674/40658). AF 95% confidence interval is 0.0395. There are 39 homozygotes in GnomAd4. There are 841 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1861 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020655.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH3	NM_020655.4	MANE Select	c.382+787_382+801dupCTGCTGCTGCTGCTG		intron	N/A	NP_065706.2
	JPH3	NM_001271604.4		c.458_472dupCTGCTGCTGCTGCTG	p.Ala153_Ala157dup	disruptive_inframe_insertion	Exon 2 of 2	NP_001258533.1
	JPH3	NM_001271605.3		c.*156_*170dupCTGCTGCTGCTGCTG		3_prime_UTR	Exon 2 of 2	NP_001258534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH3	ENST00000284262.3	TSL:1 MANE Select	c.382+787_382+801dupCTGCTGCTGCTGCTG		intron	N/A	ENSP00000284262.2
	JPH3	ENST00000301008.5	TSL:1	n.718_732dupCTGCTGCTGCTGCTG		non_coding_transcript_exon	Exon 2 of 2
	JPH3	ENST00000537256.5	TSL:2	n.96+2385_96+2399dupCTGCTGCTGCTGCTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1857 AN: 149948 Hom.: 39 Cov.: 0

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00568

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00170

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000934

Gnomad OTH AF: 0.0107

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00195 AC: 2504 AN: 1282726 Hom.: 61 Cov.: 30 AF XY: 0.00180 AC XY: 1138 AN XY: 632932

African (AFR) AF: 0.0447 AC: 1266 AN: 28294

American (AMR) AF: 0.00432 AC: 140 AN: 32394

Ashkenazi Jewish (ASJ) AF: 0.0000923 AC: 2 AN: 21658

East Asian (EAS) AF: 0.00183 AC: 44 AN: 24074

South Asian (SAS) AF: 0.00125 AC: 97 AN: 77826

European-Finnish (FIN) AF: 0.000272 AC: 8 AN: 29388

Middle Eastern (MID) AF: 0.00514 AC: 26 AN: 5060

European-Non Finnish (NFE) AF: 0.000727 AC: 736 AN: 1012974

Other (OTH) AF: 0.00362 AC: 185 AN: 51058

GnomAD4 genome AF: 0.0124 AC: 1861 AN: 150056 Hom.: 39 Cov.: 0 AF XY: 0.0115 AC XY: 841 AN XY: 73218

African (AFR) AF: 0.0412 AC: 1674 AN: 40658

American (AMR) AF: 0.00568 AC: 86 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5062

South Asian (SAS) AF: 0.00170 AC: 8 AN: 4710

European-Finnish (FIN) AF: 0.000194 AC: 2 AN: 10302

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000934 AC: 63 AN: 67458

Other (OTH) AF: 0.0111 AC: 23 AN: 2076

Alfa AF: 0.00 Hom.: 316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71156237; hg19: chr16-87637893;