rs756658

Positions:

• chr22-19468313-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005659.7(UFD1):​c.292-310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,078 control chromosomes in the GnomAD database, including 12,713 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 0.37 (12713 hom., cov: 32)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.292-310T>C		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.292-310T>C		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56120 AN: 151960 Hom.: 12703 Cov.: 32

Gnomad AFR AF: 0.0983

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.369 AC: 56136 AN: 152078 Hom.: 12713 Cov.: 32 AF XY: 0.369 AC XY: 27409 AN XY: 74344

Gnomad4 AFR AF: 0.0981

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.408

Alfa AF: 0.466 Hom.: 12905

Bravo AF: 0.350

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: -48

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs756658; hg19: chr22-19455836; COSMIC: COSV54250642; COSMIC: COSV54250642;