chr22-19468082-G-A

Position:

• chr22-19468082-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005659.7(UFD1):​c.292-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 1,553,378 control chromosomes in the GnomAD database, including 1,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (293 hom., cov: 33)
  • Exomes 𝑓: 0.029 (1248 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.327

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-19468082-G-A is Benign according to our data. Variant chr22-19468082-G-A is described in ClinVar as [Benign]. Clinvar id is 1250336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.292-79C>T		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.292-79C>T		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7603 AN: 152158 Hom.: 291 Cov.: 33

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0782

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0377

GnomAD4 exome AF: 0.0291 AC: 40834 AN: 1401102 Hom.: 1248 AF XY: 0.0302 AC XY: 20942 AN XY: 692686

Gnomad4 AFR exome AF: 0.0899

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0856

Gnomad4 FIN exome AF: 0.0428

Gnomad4 NFE exome AF: 0.0174

Gnomad4 OTH exome AF: 0.0354

GnomAD4 genome AF: 0.0500 AC: 7613 AN: 152276 Hom.: 293 Cov.: 33 AF XY: 0.0533 AC XY: 3971 AN XY: 74440

Gnomad4 AFR AF: 0.0844

Gnomad4 AMR AF: 0.0785

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0961

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0330 Hom.: 18

Bravo AF: 0.0525

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5748222; hg19: chr22-19455605;