22-19478862-G-A

Position:

• chr22-19478862-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005659.7(UFD1):​c.3+221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 576,834 control chromosomes in the GnomAD database, including 60,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12827 hom., cov: 34)
  • Exomes 𝑓: 0.47 (47881 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 22-19478862-G-A is Benign according to our data. Variant chr22-19478862-G-A is described in ClinVar as [Benign]. Clinvar id is 1247850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.3+221C>T		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.3+221C>T		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56378 AN: 152066 Hom.: 12817 Cov.: 34

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.467 AC: 198381 AN: 424650 Hom.: 47881 Cov.: 5 AF XY: 0.468 AC XY: 104544 AN XY: 223436

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.371 AC: 56394 AN: 152184 Hom.: 12827 Cov.: 34 AF XY: 0.370 AC XY: 27519 AN XY: 74416

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.413

Alfa AF: 0.430 Hom.: 1966

Bravo AF: 0.352

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5993649; hg19: chr22-19466385;