Variant chr22-19450839-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005659.7(UFD1):c.850-95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,592,428 control chromosomes in the GnomAD database, including 2,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.047 ( 217 hom., cov: 31)

Exomes 𝑓: 0.056 ( 2466 hom. )

Consequence

UFD1
NM_005659.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.351

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 22-19450839-A-G is Benign according to our data. Variant chr22-19450839-A-G is described in ClinVar as [Benign]. Clinvar id is 1264477.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7 linkuse as main transcript	c.850-95T>C		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15 linkuse as main transcript	c.850-95T>C	intron_variant		1	NM_005659.7	P1	Q92890-2
UFD1	ENST00000399523.5 linkuse as main transcript	c.797-95T>C	intron_variant		1			Q92890-3
UFD1	ENST00000459854.5 linkuse as main transcript	n.4820T>C	non_coding_transcript_exon_variant	11/11	1
UFD1	ENST00000466373.1 linkuse as main transcript	n.2940-95T>C	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0466

AC:

7085

AN:

152114

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0400

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0623

GnomAD4 exome

AF:

0.0557

AC:

80226

AN:

1440196

Hom.:

2466

Cov.:

AF XY:

0.0553

AC XY:

39505

AN XY:

714612

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.0945

Gnomad4 ASJ exome

AF:

0.0526

Gnomad4 EAS exome

AF:

0.0567

Gnomad4 SAS exome

AF:

0.0356

Gnomad4 FIN exome

AF:

0.0409

Gnomad4 NFE exome

AF:

0.0575

Gnomad4 OTH exome

AF:

0.0526

GnomAD4 genome

AF:

0.0466

AC:

7098

AN:

152232

Hom.:

217

Cov.:

AF XY:

0.0467

AC XY:

3476

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.0769

Gnomad4 ASJ

AF:

0.0528

Gnomad4 EAS

AF:

0.0423

Gnomad4 SAS

AF:

0.0311

Gnomad4 FIN

AF:

0.0400

Gnomad4 NFE

AF:

0.0581

Gnomad4 OTH

AF:

0.0621

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0510

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.9

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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