22-41619761-C-T

Variant names:

• chr22-41619761-C-T
• rs5751129
• NM_015704.3:c.88+991G>A

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+991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,068 control chromosomes in the GnomAD database, including 38,017 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 0.69 (38017 hom., cov: 32)
• Consequence: DESI1 NM_015704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• Publications: 35 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DESI1	NM_015704.3	MANE Select	c.88+991G>A		intron	N/A	NP_056519.1	Q6ICB0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DESI1	ENST00000263256.7	TSL:1 MANE Select	c.88+991G>A		intron	N/A	ENSP00000263256.6	Q6ICB0
	DESI1	ENST00000938248.1		c.88+991G>A		intron	N/A	ENSP00000608307.1
	DESI1	ENST00000881058.1		c.88+991G>A		intron	N/A	ENSP00000551117.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105170 AN: 151950 Hom.: 38011 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.692 AC: 105190 AN: 152068 Hom.: 38017 Cov.: 32 AF XY: 0.686 AC XY: 50974 AN XY: 74332

African (AFR) AF: 0.516 AC: 21388 AN: 41442

American (AMR) AF: 0.544 AC: 8305 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2443 AN: 3472

East Asian (EAS) AF: 0.917 AC: 4752 AN: 5182

South Asian (SAS) AF: 0.652 AC: 3144 AN: 4820

European-Finnish (FIN) AF: 0.742 AC: 7841 AN: 10564

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 55016 AN: 67994

Other (OTH) AF: 0.694 AC: 1469 AN: 2116

Alfa AF: 0.743 Hom.: 13554

Bravo AF: 0.665

Asia WGS AF: 0.767 AC: 2666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.76
PhyloP100		0.81
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: rs5751129; hg19: chr22-42015765;