chr22-19471634-A-C

Variant names:

• chr22-19471634-A-C
• rs2073758
• NM_005659.7:c.291+53T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005659.7(UFD1):​c.291+53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,443,486 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 12 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	NM_005659.7	MANE Select	c.291+53T>G		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.276+53T>G		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.291+53T>G		intron	N/A	NP_001030324.2	Q92890-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	ENST00000263202.15	TSL:1 MANE Select	c.291+53T>G		intron	N/A	ENSP00000263202.9	Q92890-2
	UFD1	ENST00000399523.5	TSL:1	c.291+53T>G		intron	N/A	ENSP00000382439.1	Q92890-3
	UFD1	ENST00000459854.5	TSL:1	n.352+53T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1443486 Hom.: 0 AF XY: 0.00000140 AC XY: 1 AN XY: 716726

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.00 AC: 0 AN: 43516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25074

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39512

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103546

Other (OTH) AF: 0.0000168 AC: 1 AN: 59518

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.42
PhyloP100		0.22

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: rs2073758; hg19: chr22-19459157;