22-19478942-C-G

Position:

• chr22-19478942-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005659.7(UFD1):​c.3+141G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,169,476 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 33)
  • Exomes 𝑓: 0.012 (128 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-19478942-C-G is Benign according to our data. Variant chr22-19478942-C-G is described in ClinVar as [Benign]. Clinvar id is 1261224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.3+141G>C		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.3+141G>C		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1659 AN: 152188 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0116 AC: 11825 AN: 1017172 Hom.: 128 Cov.: 13 AF XY: 0.0117 AC XY: 5952 AN XY: 507886

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.00376

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.0000668

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.0540

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.0109 AC: 1656 AN: 152304 Hom.: 21 Cov.: 33 AF XY: 0.0127 AC XY: 946 AN XY: 74480

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00953

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0102 Hom.: 3

Bravo AF: 0.00683

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.8
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs151336351; hg19: chr22-19466465;