22-19467974-G-A

Variant names:

• chr22-19467974-G-A
• rs34958629
• NM_005659.7:c.321C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_005659.7(UFD1):​c.321C>T​(p.Gly107Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000952 in 1,614,116 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (6 hom.)
• Consequence: UFD1 NM_005659.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.629
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 22-19467974-G-A is Benign according to our data. Variant chr22-19467974-G-A is described in ClinVar as Benign. ClinVar VariationId is 786375.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.629 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00523 (797/152260) while in subpopulation AFR AF = 0.0176 (730/41556). AF 95% confidence interval is 0.0165. There are 7 homozygotes in GnomAd4. There are 387 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

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.321C>T	p.Gly107Gly	synonymous	Exon 5 of 12	NP_005650.2
	UFD1	NM_001362910.2		c.306C>T	p.Gly102Gly	synonymous	Exon 5 of 12	NP_001349839.1
	UFD1	NM_001035247.3		c.321C>T	p.Gly107Gly	synonymous	Exon 5 of 12	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.321C>T	p.Gly107Gly	synonymous	Exon 5 of 12	ENSP00000263202.9	Q92890-2
	UFD1	ENST00000399523.5	TSL:1	c.321C>T	p.Gly107Gly	synonymous	Exon 5 of 12	ENSP00000382439.1	Q92890-3
	UFD1	ENST00000459854.5	TSL:1	n.382C>T		non_coding_transcript_exon	Exon 5 of 11

Frequencies

GnomAD3 genomes AF: 0.00524 AC: 797 AN: 152142 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00150 AC: 378 AN: 251442 AF XY: 0.00108

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000506 AC: 740 AN: 1461856 Hom.: 6 Cov.: 32 AF XY: 0.000462 AC XY: 336 AN XY: 727234

African (AFR) AF: 0.0177 AC: 593 AN: 33478

American (AMR) AF: 0.00141 AC: 63 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111992

Other (OTH) AF: 0.00119 AC: 72 AN: 60394

GnomAD4 genome AF: 0.00523 AC: 797 AN: 152260 Hom.: 7 Cov.: 33 AF XY: 0.00520 AC XY: 387 AN XY: 74452

African (AFR) AF: 0.0176 AC: 730 AN: 41556

American (AMR) AF: 0.00353 AC: 54 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00241 Hom.: 1

Bravo AF: 0.00617

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	UFD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.3
DANN	Benign	0.59
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34958629; hg19: chr22-19455497;