NM_005659.7:c.850-95T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005659.7(UFD1):​c.850-95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,592,428 control chromosomes in the GnomAD database, including 2,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (217 hom., cov: 31)
  • Exomes 𝑓: 0.056 (2466 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 22-19450839-A-G is Benign according to our data. Variant chr22-19450839-A-G is described in ClinVar as Benign. ClinVar VariationId is 1264477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0733 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>C		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.835-95T>C		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.797-95T>C		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>C		intron	N/A	ENSP00000263202.9	Q92890-2
	UFD1	ENST00000399523.5	TSL:1	c.797-95T>C		intron	N/A	ENSP00000382439.1	Q92890-3
	UFD1	ENST00000459854.5	TSL:1	n.4820T>C		non_coding_transcript_exon	Exon 11 of 11

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7085 AN: 152114 Hom.: 217 Cov.: 31

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0623

GnomAD4 exome AF: 0.0557 AC: 80226 AN: 1440196 Hom.: 2466 Cov.: 30 AF XY: 0.0553 AC XY: 39505 AN XY: 714612

African (AFR) AF: 0.0179 AC: 589 AN: 32846

American (AMR) AF: 0.0945 AC: 4093 AN: 43308

Ashkenazi Jewish (ASJ) AF: 0.0526 AC: 1335 AN: 25400

East Asian (EAS) AF: 0.0567 AC: 2217 AN: 39118

South Asian (SAS) AF: 0.0356 AC: 3028 AN: 85096

European-Finnish (FIN) AF: 0.0409 AC: 2071 AN: 50668

Middle Eastern (MID) AF: 0.104 AC: 590 AN: 5652

European-Non Finnish (NFE) AF: 0.0575 AC: 63185 AN: 1098812

Other (OTH) AF: 0.0526 AC: 3118 AN: 59296

GnomAD4 genome AF: 0.0466 AC: 7098 AN: 152232 Hom.: 217 Cov.: 31 AF XY: 0.0467 AC XY: 3476 AN XY: 74436

African (AFR) AF: 0.0195 AC: 810 AN: 41544

American (AMR) AF: 0.0769 AC: 1176 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3468

East Asian (EAS) AF: 0.0423 AC: 219 AN: 5174

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4828

European-Finnish (FIN) AF: 0.0400 AC: 424 AN: 10610

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0581 AC: 3954 AN: 68002

Other (OTH) AF: 0.0621 AC: 131 AN: 2110

Alfa AF: 0.0189 Hom.: 12

Bravo AF: 0.0510

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.9
DANN	Benign	0.58
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV54250486; COSMIC: COSV54250486;