22-19468082-G-A

Variant names:

• chr22-19468082-G-A
• rs5748222
• NM_005659.7:c.292-79C>T

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.292-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 1,553,378 control chromosomes in the GnomAD database, including 1,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (293 hom., cov: 33)
  • Exomes 𝑓: 0.029 (1248 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.327
• 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-19468082-G-A is Benign according to our data. Variant chr22-19468082-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 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.292-79C>T		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.277-79C>T		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.292-79C>T		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.292-79C>T		intron	N/A	ENSP00000263202.9	Q92890-2
	UFD1	ENST00000399523.5	TSL:1	c.292-79C>T		intron	N/A	ENSP00000382439.1	Q92890-3
	UFD1	ENST00000459854.5	TSL:1	n.353-79C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7603 AN: 152158 Hom.: 291 Cov.: 33

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0782

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0377

GnomAD4 exome AF: 0.0291 AC: 40834 AN: 1401102 Hom.: 1248 AF XY: 0.0302 AC XY: 20942 AN XY: 692686

African (AFR) AF: 0.0899 AC: 2789 AN: 31030

American (AMR) AF: 0.106 AC: 3645 AN: 34522

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 401 AN: 22834

East Asian (EAS) AF: 0.109 AC: 4224 AN: 38856

South Asian (SAS) AF: 0.0856 AC: 6689 AN: 78098

European-Finnish (FIN) AF: 0.0428 AC: 2160 AN: 50458

Middle Eastern (MID) AF: 0.0145 AC: 79 AN: 5462

European-Non Finnish (NFE) AF: 0.0174 AC: 18805 AN: 1082226

Other (OTH) AF: 0.0354 AC: 2042 AN: 57616

GnomAD4 genome AF: 0.0500 AC: 7613 AN: 152276 Hom.: 293 Cov.: 33 AF XY: 0.0533 AC XY: 3971 AN XY: 74440

African (AFR) AF: 0.0844 AC: 3507 AN: 41558

American (AMR) AF: 0.0785 AC: 1201 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3472

East Asian (EAS) AF: 0.118 AC: 608 AN: 5172

South Asian (SAS) AF: 0.0961 AC: 463 AN: 4816

European-Finnish (FIN) AF: 0.0534 AC: 566 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1131 AN: 68030

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0358 Hom.: 21

Bravo AF: 0.0525

Asia WGS AF: 0.107 AC: 371 AN: 3478

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	-0.81
CADD	Benign	8.4
DANN	Benign	0.69
PhyloP100		0.33
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: rs5748222; hg19: chr22-19455605; COSMIC: COSV107202906; COSMIC: COSV107202906;