Variant chr22-19467853-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005659.7(UFD1):c.422+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,612,910 control chromosomes in the GnomAD database, including 224,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20708 hom., cov: 33)

Exomes 𝑓: 0.53 ( 203353 hom. )

Consequence

UFD1
NM_005659.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.416

Variant links:

Genes affected

UFD1 (HGNC:12520): (ubiquitin recognition factor in ER associated degradation 1) The protein encoded by this gene forms a complex with two other proteins, nuclear protein localization-4 and valosin-containing protein, and this complex is necessary for the degradation of ubiquitinated proteins. In addition, this complex controls the disassembly of the mitotic spindle and the formation of a closed nuclear envelope after mitosis. Mutations in this gene have been associated with Catch 22 syndrome as well as cardiac and craniofacial defects. Alternative splicing results in multiple transcript variants encoding different isoforms. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Jun 2009]

UFD1 links:

UFD1 (HGNC:):

UFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-19467853-C-T is Benign according to our data. Variant chr22-19467853-C-T is described in ClinVar as [Benign]. Clinvar id is 1227804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19467853-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UFD1	NM_005659.7 linkuse as main transcript	c.422+20G>A		intron_variant		ENST00000263202.15	NP_005650.2	Q92890-2Q541A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UFD1	ENST00000263202.15 linkuse as main transcript	c.422+20G>A		intron_variant		1	NM_005659.7	ENSP00000263202.9		Q92890-2

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79028

AN:

151988

Hom.:

20686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.532

GnomAD3 exomes

AF:

0.518

AC:

129928

AN:

251048

Hom.:

34226

AF XY:

0.527

AC XY:

71510

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.611

Gnomad EAS exome

AF:

0.385

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.482

Gnomad NFE exome

AF:

0.530

Gnomad OTH exome

AF:

0.537

GnomAD4 exome

AF:

0.525

AC:

767549

AN:

1460804

Hom.:

203353

Cov.:

AF XY:

0.528

AC XY:

383985

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.462

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.615

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.536

GnomAD4 genome

AF:

0.520

AC:

79088

AN:

152106

Hom.:

20708

Cov.:

AF XY:

0.518

AC XY:

38505

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.509

Gnomad4 ASJ

AF:

0.622

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.605

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.525

Hom.:

32796

Bravo

AF:

0.516

Asia WGS

AF:

0.503

AC:

1749

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.44

DANN

Benign

0.39

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