22-19466204-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005659.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	NM_005659.7	MANE Select	c.423-930G>C		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.408-930G>C		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.423-930G>C		intron	N/A	NP_001030324.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	ENST00000263202.15	TSL:1 MANE Select	c.423-930G>C		intron	N/A	ENSP00000263202.9
	UFD1	ENST00000399523.5	TSL:1	c.423-930G>C		intron	N/A	ENSP00000382439.1
	UFD1	ENST00000459854.5	TSL:1	n.484-930G>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.571 AC: 8 AN: 14

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.182 AC: 7570 AN: 41522

American (AMR) AF: 0.179 AC: 2742 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3468

East Asian (EAS) AF: 0.312 AC: 1610 AN: 5162

South Asian (SAS) AF: 0.157 AC: 760 AN: 4826

European-Finnish (FIN) AF: 0.212 AC: 2243 AN: 10582

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13286 AN: 67976

Other (OTH) AF: 0.174 AC: 368 AN: 2114

Alfa AF: 0.106 Hom.: 170

Bravo AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2238769; hg19: chr22-19453727;