22-19473143-C-G

Variant names:

• chr22-19473143-C-G
• rs1547931
• NM_005659.7:c.170-1335G>C

Variant summary

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

The NM_005659.7(UFD1):​c.170-1335G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,178 control chromosomes in the GnomAD database, including 58,583 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 0.88 (58583 hom., cov: 31)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 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.170-1335G>C		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.155-1335G>C		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.170-1335G>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.170-1335G>C		intron	N/A	ENSP00000263202.9	Q92890-2
	UFD1	ENST00000399523.5	TSL:1	c.170-1335G>C		intron	N/A	ENSP00000382439.1	Q92890-3
	UFD1	ENST00000459854.5	TSL:1	n.231-1335G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133118 AN: 152060 Hom.: 58525 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.870

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.876 AC: 133237 AN: 152178 Hom.: 58583 Cov.: 31 AF XY: 0.875 AC XY: 65072 AN XY: 74382

African (AFR) AF: 0.962 AC: 39953 AN: 41546

American (AMR) AF: 0.882 AC: 13494 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2983 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4408 AN: 5142

South Asian (SAS) AF: 0.924 AC: 4457 AN: 4824

European-Finnish (FIN) AF: 0.800 AC: 8460 AN: 10570

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56610 AN: 68006

Other (OTH) AF: 0.871 AC: 1842 AN: 2114

Alfa AF: 0.816 Hom.: 2498

Bravo AF: 0.882

Asia WGS AF: 0.894 AC: 3109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.70
DANN	Benign	0.36
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1547931;

hg19: chr22-19460666;