Genetic Variant UFD1:c.422+20G>A (chr22-19467853-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

15 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1227804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005659.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UFD1	NM_005659.7	MANE Select	c.422+20G>A	intron	N/A	NP_005650.2
UFD1	NM_001362910.2		c.407+20G>A	intron	N/A	NP_001349839.1
UFD1	NM_001035247.3		c.422+20G>A	intron	N/A	NP_001030324.2	Q92890-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UFD1	ENST00000263202.15	TSL:1 MANE Select	c.422+20G>A	intron	N/A	ENSP00000263202.9	Q92890-2
UFD1	ENST00000399523.5	TSL:1	c.422+20G>A	intron	N/A	ENSP00000382439.1	Q92890-3
UFD1	ENST00000459854.5	TSL:1	n.483+20G>A	intron	N/A

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

GnomAD2 exomes

AF:

0.518

AC:

129928

AN:

251048

AF XY:

0.527

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 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

African (AFR)

AF:

0.502

AC:

16778

AN:

33450

American (AMR)

AF:

0.462

AC:

20635

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

15836

AN:

26108

East Asian (EAS)

AF:

0.347

AC:

13783

AN:

39676

South Asian (SAS)

AF:

0.615

AC:

53035

AN:

86206

European-Finnish (FIN)

AF:

0.490

AC:

26153

AN:

53348

Middle Eastern (MID)

AF:

0.590

AC:

3189

AN:

5402

European-Non Finnish (NFE)

AF:

0.527

AC:

585844

AN:

1111636

Other (OTH)

AF:

0.536

AC:

32296

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

19200

38400

57600

76800

96000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16774

33548

50322

67096

83870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.520

AC:

79088

AN:

152106

Hom.:

20708

Cov.:

AF XY:

0.518

AC XY:

38505

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.509

AC:

21130

AN:

41480

American (AMR)

AF:

0.509

AC:

7790

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2158

AN:

3470

East Asian (EAS)

AF:

0.381

AC:

1967

AN:

5164

South Asian (SAS)

AF:

0.605

AC:

2921

AN:

4826

European-Finnish (FIN)

AF:

0.481

AC:

5078

AN:

10562

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36249

AN:

67996

Other (OTH)

AF:

0.538

AC:

1134

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2004

4008

6012

8016

10020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.525

Hom.:

45476

Bravo

AF:

0.516

Asia WGS

AF:

0.503

AC:

1749

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.44

(source)

DANN

Benign

0.39

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over