22-19450839-A-C

Variant names:

• chr22-19450839-A-C
• rs5748208
• NM_005659.7:c.850-95T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005659.7(UFD1):​c.850-95T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 1,592,466 control chromosomes in the GnomAD database, including 2,047 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 0.030 (148 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1899 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• Publications: 2 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]

UFD1-AS1 (HGNC:55917): (UFD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

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.850-95T>G		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.835-95T>G		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.797-95T>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.850-95T>G		intron	N/A	ENSP00000263202.9	Q92890-2
	UFD1	ENST00000399523.5	TSL:1	c.797-95T>G		intron	N/A	ENSP00000382439.1	Q92890-3
	UFD1	ENST00000459854.5	TSL:1	n.4820T>G		non_coding_transcript_exon	Exon 11 of 11

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4538 AN: 152108 Hom.: 150 Cov.: 31

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0176

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0398

GnomAD4 exome AF: 0.0384 AC: 55255 AN: 1440240 Hom.: 1899 Cov.: 30 AF XY: 0.0414 AC XY: 29580 AN XY: 714660

African (AFR) AF: 0.00472 AC: 155 AN: 32846

American (AMR) AF: 0.0474 AC: 2051 AN: 43306

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4234 AN: 25386

East Asian (EAS) AF: 0.0162 AC: 633 AN: 39124

South Asian (SAS) AF: 0.129 AC: 11009 AN: 85082

European-Finnish (FIN) AF: 0.00969 AC: 491 AN: 50674

Middle Eastern (MID) AF: 0.0856 AC: 484 AN: 5652

European-Non Finnish (NFE) AF: 0.0305 AC: 33466 AN: 1098880

Other (OTH) AF: 0.0461 AC: 2732 AN: 59290

GnomAD4 genome AF: 0.0298 AC: 4533 AN: 152226 Hom.: 148 Cov.: 31 AF XY: 0.0311 AC XY: 2312 AN XY: 74434

African (AFR) AF: 0.00580 AC: 241 AN: 41544

American (AMR) AF: 0.0403 AC: 616 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3470

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5170

South Asian (SAS) AF: 0.128 AC: 619 AN: 4828

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10610

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0310 AC: 2105 AN: 68004

Other (OTH) AF: 0.0398 AC: 84 AN: 2110

Alfa AF: 0.00414 Hom.: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.7
DANN	Benign	0.58
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5748208; hg19: chr22-19438362;