chr22-38699693-C-G

Position:

• chr22-38699693-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001360236.2(JOSD1):​c.185+110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,030,820 control chromosomes in the GnomAD database, including 56,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11116 hom., cov: 32)
  • Exomes 𝑓: 0.32 (45830 hom.)
• Consequence: JOSD1 NM_001360236.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

Genes affected

JOSD1 (HGNC:28953): (Josephin domain containing 1) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JOSD1	NM_001360236.2	c.185+110G>C		intron_variant		ENST00000683374.1	NP_001347165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JOSD1	ENST00000683374.1	c.185+110G>C		intron_variant			NM_001360236.2	ENSP00000506752	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56341 AN: 151936 Hom.: 11099 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.316 AC: 277934 AN: 878766 Hom.: 45830 AF XY: 0.315 AC XY: 144172 AN XY: 457954

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.371 AC: 56404 AN: 152054 Hom.: 11116 Cov.: 32 AF XY: 0.369 AC XY: 27409 AN XY: 74314

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.343

Alfa AF: 0.347 Hom.: 1230

Bravo AF: 0.371

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs926299; hg19: chr22-39095698;