22-19474943-C-T

Variant names:

• chr22-19474943-C-T
• rs5746744
• NM_005659.7:c.169+125G>A

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.169+125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 29)
  • Exomes 𝑓: 0.0000048 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 4 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=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UFD1	NM_005659.7	c.169+125G>A		intron_variant	Intron 3 of 11	ENST00000263202.15	NP_005650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UFD1	ENST00000263202.15	c.169+125G>A		intron_variant	Intron 3 of 11	1	NM_005659.7	ENSP00000263202.9

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000475 AC: 4 AN: 841962 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 431206

African (AFR) AF: 0.00 AC: 0 AN: 18796

American (AMR) AF: 0.00 AC: 0 AN: 25026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16452

East Asian (EAS) AF: 0.00 AC: 0 AN: 32562

South Asian (SAS) AF: 0.0000196 AC: 1 AN: 51000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2598

European-Non Finnish (NFE) AF: 0.00000490 AC: 3 AN: 611928

Other (OTH) AF: 0.00 AC: 0 AN: 37246

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 2973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.90
PhyloP100		0.031

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: rs5746744; hg19: chr22-19462466;