Genetic Variant NM_005659.7:c.291+53T>C (chr22-19471634-A-G) – 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.291+53T>C 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 1,594,598 control chromosomes in the GnomAD database, including 221,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20712 hom., cov: 31)

Exomes 𝑓: 0.53 ( 201030 hom. )

Consequence

UFD1
NM_005659.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.220

Publications

12 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:

Genome browser will be placed here

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=-0.9).

BP6

Variant 22-19471634-A-G is Benign according to our data. Variant chr22-19471634-A-G is described in ClinVar as Benign. ClinVar VariationId is 1229066.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.291+53T>C	intron	N/A	NP_005650.2
UFD1	NM_001362910.2		c.276+53T>C	intron	N/A	NP_001349839.1
UFD1	NM_001035247.3		c.291+53T>C	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.291+53T>C	intron	N/A	ENSP00000263202.9	Q92890-2
UFD1	ENST00000399523.5	TSL:1	c.291+53T>C	intron	N/A	ENSP00000382439.1	Q92890-3
UFD1	ENST00000459854.5	TSL:1	n.352+53T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78982

AN:

151856

Hom.:

20690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.526

AC:

758364

AN:

1442624

Hom.:

201030

AF XY:

0.529

AC XY:

378594

AN XY:

716304

show subpopulations

African (AFR)

AF:

0.503

AC:

16654

AN:

33104

American (AMR)

AF:

0.464

AC:

20153

AN:

43478

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

15195

AN:

25056

East Asian (EAS)

AF:

0.347

AC:

13698

AN:

39500

South Asian (SAS)

AF:

0.615

AC:

51939

AN:

84414

European-Finnish (FIN)

AF:

0.490

AC:

24668

AN:

50348

Middle Eastern (MID)

AF:

0.587

AC:

2505

AN:

4270

European-Non Finnish (NFE)

AF:

0.527

AC:

581647

AN:

1102952

Other (OTH)

AF:

0.536

AC:

31905

AN:

59502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

17302

34603

51905

69206

86508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16744

33488

50232

66976

83720

<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:

79043

AN:

151974

Hom.:

20712

Cov.:

AF XY:

0.518

AC XY:

38463

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.510

AC:

21128

AN:

41434

American (AMR)

AF:

0.509

AC:

7779

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2157

AN:

3470

East Asian (EAS)

AF:

0.381

AC:

1961

AN:

5150

South Asian (SAS)

AF:

0.605

AC:

2908

AN:

4806

European-Finnish (FIN)

AF:

0.480

AC:

5063

AN:

10556

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36250

AN:

67966

Other (OTH)

AF:

0.538

AC:

1136

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1914

3827

5741

7654

9568

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:

0.534

Hom.:

11187

Bravo

AF:

0.516

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

-0.90

CADD

Benign

0.94

(source)

DANN

Benign

0.36

PhyloP100

0.22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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