Variant chr22-41604068-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015704.3(DESI1):c.266C>T(p.Ser89Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,613,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

DESI1
NM_015704.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.05

Variant links:

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]

DESI1 links:

DESI1 (HGNC:):

DESI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17403492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DESI1	NM_015704.3 linkuse as main transcript	c.266C>T	p.Ser89Phe	missense_variant	4/6	ENST00000263256.7	NP_056519.1	Q6ICB0
DESI1	XM_047441335.1 linkuse as main transcript	c.194C>T	p.Ser65Phe	missense_variant	5/7		XP_047297291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DESI1	ENST00000263256.7 linkuse as main transcript	c.266C>T	p.Ser89Phe	missense_variant	4/6	1	NM_015704.3	ENSP00000263256.6	Q6ICB0
DESI1	ENST00000463886.1 linkuse as main transcript	n.158C>T		non_coding_transcript_exon_variant	1/3	2
DESI1	ENST00000482612.1 linkuse as main transcript	n.20C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000957

AC:

AN:

250658

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

193

AN:

1461626

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000125

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000157

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.266C>T (p.S89F) alteration is located in exon 4 (coding exon 4) of the DESI1 gene. This alteration results from a C to T substitution at nucleotide position 266, causing the serine (S) at amino acid position 89 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0059

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.20

Sift

Uncertain

0.014

Sift4G

Uncertain

0.028

Polyphen

0.011

Vest4

0.27

MVP

0.41

MPC

0.60

ClinPred

0.21

GERP RS

5.7

Varity_R

0.59

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over