22-19473143-C-G

Position:

• chr22-19473143-C-G

Variant summary

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

The NM_005659.7(UFD1):​c.170-1335G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,178 control chromosomes in the GnomAD database, including 58,583 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 0.88 (58583 hom., cov: 31)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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]

UFD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• 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	Protein	UniProt
UFD1	NM_005659.7	c.170-1335G>C		intron_variant		ENST00000263202.15	NP_005650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UFD1	ENST00000263202.15	c.170-1335G>C		intron_variant		1	NM_005659.7	ENSP00000263202.9

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133118 AN: 152060 Hom.: 58525 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.860

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: 0.870

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.876 AC: 133237 AN: 152178 Hom.: 58583 Cov.: 31 AF XY: 0.875 AC XY: 65072 AN XY: 74382

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.871

Alfa AF: 0.816 Hom.: 2498

Bravo AF: 0.882

Asia WGS AF: 0.894 AC: 3109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.70
DANN	Benign	0.36

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: rs1547931; hg19: chr22-19460666;