chr22-19466204-C-G

Variant names:

• chr22-19466204-C-G
• rs2238769
• NM_005659.7:c.423-930G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005659.7(UFD1):​c.423-930G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,166 control chromosomes in the GnomAD database, including 2,905 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2901 hom., cov: 33)
  • Exomes 𝑓: 0.42 (4 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UFD1	NM_005659.7	c.423-930G>C		intron_variant	Intron 5 of 11	ENST00000263202.15	NP_005650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UFD1	ENST00000263202.15	c.423-930G>C		intron_variant	Intron 5 of 11	1	NM_005659.7	ENSP00000263202.9

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29261 AN: 152024 Hom.: 2903 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.417 AC: 10 AN: 24 Hom.: 4 Cov.: 0 AF XY: 0.417 AC XY: 10 AN XY: 24

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.571

GnomAD4 genome AF: 0.192 AC: 29263 AN: 152142 Hom.: 2901 Cov.: 33 AF XY: 0.193 AC XY: 14349 AN XY: 74396

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.174

Alfa AF: 0.106 Hom.: 170

Bravo AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.44

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: rs2238769; hg19: chr22-19453727;