22-19471634-A-G

Position:

• chr22-19471634-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.220

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UFD1	NM_005659.7	c.291+53T>C		intron_variant		ENST00000263202.15	NP_005650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UFD1	ENST00000263202.15	c.291+53T>C		intron_variant		1	NM_005659.7	ENSP00000263202.9

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78982 AN: 151856 Hom.: 20690 Cov.: 31

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

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.520 AC: 79043 AN: 151974 Hom.: 20712 Cov.: 31 AF XY: 0.518 AC XY: 38463 AN XY: 74256

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.538

Alfa AF: 0.535 Hom.: 9975

Bravo AF: 0.516

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	-0.90
CADD	Benign	0.94
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs2073758; hg19: chr22-19459157;