chr22-19456408-G-T

Position:

• chr22-19456408-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005659.7(UFD1):​c.678+179C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 757,744 control chromosomes in the GnomAD database, including 1,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (283 hom., cov: 32)
  • Exomes 𝑓: 0.036 (802 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.734

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-19456408-G-T is Benign according to our data. Variant chr22-19456408-G-T is described in ClinVar as [Benign]. Clinvar id is 1253888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.678+179C>A		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.678+179C>A		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7498 AN: 152088 Hom.: 281 Cov.: 32

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0356 AC: 21576 AN: 605538 Hom.: 802 AF XY: 0.0372 AC XY: 11790 AN XY: 317148

Gnomad4 AFR exome AF: 0.0830

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.0861

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0349

GnomAD4 genome AF: 0.0493 AC: 7508 AN: 152206 Hom.: 283 Cov.: 32 AF XY: 0.0528 AC XY: 3928 AN XY: 74436

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.0782

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0395 Hom.: 29

Bravo AF: 0.0520

Asia WGS AF: 0.107 AC: 371 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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.50

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: rs5748212; hg19: chr22-19443931;