22-41615960-A-G

Variant names:

• chr22-41615960-A-G
• rs6002421
• NM_015704.3:c.88+4792T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015704.3(DESI1):​c.88+4792T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,206 control chromosomes in the GnomAD database, including 4,056 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 0.14 (4056 hom., cov: 32)
• Consequence: DESI1 NM_015704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 3 publications found

Genes affected

DESI1 (HGNC:24577): (desumoylating isopeptidase 1) Enables importin-alpha family protein binding activity. Involved in protein export from nucleus and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in cytosol. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015704.3. 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
	DESI1	NM_015704.3	MANE Select	c.88+4792T>C		intron	N/A	NP_056519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DESI1	ENST00000263256.7	TSL:1 MANE Select	c.88+4792T>C		intron	N/A	ENSP00000263256.6

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21130 AN: 152088 Hom.: 4021 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21222 AN: 152206 Hom.: 4056 Cov.: 32 AF XY: 0.136 AC XY: 10109 AN XY: 74416

African (AFR) AF: 0.436 AC: 18091 AN: 41492

American (AMR) AF: 0.0990 AC: 1513 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.0256 AC: 133 AN: 5194

South Asian (SAS) AF: 0.0467 AC: 225 AN: 4822

European-Finnish (FIN) AF: 0.0209 AC: 222 AN: 10604

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 731 AN: 68018

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.00526 Hom.: 8

Bravo AF: 0.159

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.32
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs6002421; hg19: chr22-42011964;