rs756658

Variant names:

• chr22-19468313-A-G
• rs756658
• NM_005659.7:c.292-310T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 -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 rank	MANE	Protein	UniProt
UFD1	NM_005659.7	c.292-310T>C		intron_variant	Intron 4 of 11	ENST00000263202.15	NP_005650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UFD1	ENST00000263202.15	c.292-310T>C		intron_variant	Intron 4 of 11	1	NM_005659.7	ENSP00000263202.9

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

African (AFR) AF: 0.0981 AC: 4071 AN: 41512

American (AMR) AF: 0.420 AC: 6414 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3468

East Asian (EAS) AF: 0.294 AC: 1519 AN: 5164

South Asian (SAS) AF: 0.447 AC: 2155 AN: 4818

European-Finnish (FIN) AF: 0.467 AC: 4936 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34020 AN: 67970

Other (OTH) AF: 0.408 AC: 860 AN: 2106

Alfa AF: 0.425 Hom.: 19826

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
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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