rs758064157

Variant names:

• chr22-38688942-C-G
• rs758064157
• NM_001360236.2:c.502G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-38688942-C-G
• chr22-38688942-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001360236.2(JOSD1):​c.502G>C​(p.Glu168Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E168K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: JOSD1 NM_001360236.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JOSD1	NM_001360236.2	MANE Select	c.502G>C	p.Glu168Gln	missense	Exon 4 of 5	NP_001347165.1	Q15040
	JOSD1	NM_001360235.2		c.502G>C	p.Glu168Gln	missense	Exon 4 of 5	NP_001347164.1	Q15040
	JOSD1	NM_014876.7		c.502G>C	p.Glu168Gln	missense	Exon 4 of 5	NP_055691.1	Q15040

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JOSD1	ENST00000683374.1	MANE Select	c.502G>C	p.Glu168Gln	missense	Exon 4 of 5	ENSP00000506752.1	Q15040
	JOSD1	ENST00000216039.9	TSL:1	c.502G>C	p.Glu168Gln	missense	Exon 3 of 4	ENSP00000216039.5	Q15040
	JOSD1	ENST00000866135.1		c.502G>C	p.Glu168Gln	missense	Exon 4 of 5	ENSP00000536194.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460854 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726656

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111472

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.92	L
PhyloP100		7.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.28	T
Sift4G	Benign	0.28	T
Polyphen		0.045	B
Vest4		0.72
MutPred		0.50		Gain of MoRF binding (P = 0.0239)
MVP		0.66
MPC		0.81
ClinPred		0.62	D
GERP RS		5.6
Varity_R		0.37
gMVP		0.68
Mutation Taster		=60/40	polymorphism

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: rs758064157; hg19: chr22-39084947;