rs926299

Variant names:

• chr22-38699693-C-A
• rs926299
• NM_001360236.2:c.185+110G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38699693-C-A
• chr22-38699693-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001360236.2(JOSD1):​c.185+110G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JOSD1 NM_001360236.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• Publications: 14 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360236.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JOSD1	NM_001360236.2	MANE Select	c.185+110G>T		intron	N/A	NP_001347165.1
	JOSD1	NM_001360235.2		c.185+110G>T		intron	N/A	NP_001347164.1
	JOSD1	NM_014876.7		c.185+110G>T		intron	N/A	NP_055691.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JOSD1	ENST00000683374.1	MANE Select	c.185+110G>T		intron	N/A	ENSP00000506752.1
	JOSD1	ENST00000216039.9	TSL:1	c.185+110G>T		intron	N/A	ENSP00000216039.5
	JOSD1	ENST00000545590.1	TSL:3	c.167+110G>T		intron	N/A	ENSP00000444798.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 880558 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 458842

African (AFR) AF: 0.00 AC: 0 AN: 21204

American (AMR) AF: 0.00 AC: 0 AN: 36770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20538

East Asian (EAS) AF: 0.00 AC: 0 AN: 36920

South Asian (SAS) AF: 0.00 AC: 0 AN: 70104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2964

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 599670

Other (OTH) AF: 0.00 AC: 0 AN: 40952

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-0.26
PromoterAI		-0.011	Neutral

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

Other links and lift over

dbSNP: rs926299; hg19: chr22-39095698;