rs5746744

Positions:

• chr22-19474943-C-G
• chr22-19474943-C-T

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.169+125G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 992,450 control chromosomes in the GnomAD database, including 355,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.88 (58511 hom., cov: 29)
  • Exomes 𝑓: 0.84 (296586 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0310

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=-0.89).
• BP6: Variant 22-19474943-C-G is Benign according to our data. Variant chr22-19474943-C-G is described in ClinVar as [Benign]. Clinvar id is 1255296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.169+125G>C		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.169+125G>C		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 132981 AN: 151930 Hom.: 58453 Cov.: 29

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.869

GnomAD4 exome AF: 0.839 AC: 705236 AN: 840402 Hom.: 296586 AF XY: 0.842 AC XY: 362353 AN XY: 430466

Gnomad4 AFR exome AF: 0.966

Gnomad4 AMR exome AF: 0.886

Gnomad4 ASJ exome AF: 0.853

Gnomad4 EAS exome AF: 0.824

Gnomad4 SAS exome AF: 0.922

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.829

Gnomad4 OTH exome AF: 0.855

GnomAD4 genome AF: 0.875 AC: 133100 AN: 152048 Hom.: 58511 Cov.: 29 AF XY: 0.875 AC XY: 65002 AN XY: 74318

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.871

Alfa AF: 0.828 Hom.: 2973

Bravo AF: 0.882

Asia WGS AF: 0.894 AC: 3108 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 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.63

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: rs5746744; hg19: chr22-19462466;