Variant chr22-19450821-G-A 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.850-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,606,858 control chromosomes in the GnomAD database, including 3,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.085 ( 1825 hom., cov: 31)

Exomes 𝑓: 0.0090 ( 1638 hom. )

Consequence

UFD1
NM_005659.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.938

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-19450821-G-A is Benign according to our data. Variant chr22-19450821-G-A is described in ClinVar as [Benign]. Clinvar id is 1236720.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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.850-77C>T		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15 linkuse as main transcript	c.850-77C>T	intron_variant		1	NM_005659.7	P1	Q92890-2
UFD1	ENST00000399523.5 linkuse as main transcript	c.797-77C>T	intron_variant		1			Q92890-3
UFD1	ENST00000459854.5 linkuse as main transcript	n.4838C>T	non_coding_transcript_exon_variant	11/11	1
UFD1	ENST00000466373.1 linkuse as main transcript	n.2940-77C>T	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0853

AC:

12951

AN:

151908

Hom.:

1822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0346

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.0665

GnomAD4 exome

AF:

0.00895

AC:

13028

AN:

1454832

Hom.:

1638

Cov.:

AF XY:

0.00773

AC XY:

5592

AN XY:

723162

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.00332

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000628

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.000628

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0853

AC:

12974

AN:

152026

Hom.:

1825

Cov.:

AF XY:

0.0821

AC XY:

6105

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.0658

Alfa

AF:

0.0815

Hom.:

301

Bravo

AF:

0.0971

Asia WGS

AF:

0.0170

AC:

AN:

3478

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.8

DANN

Benign

0.72

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