NM_020131.5:c.*756A>G

Variant names:

• chr1-156036222-T-C
• rs3820592
• NM_020131.5:c.*756A>G

Variant summary

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

The NM_020131.5(UBQLN4):​c.*756A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 985,378 control chromosomes in the GnomAD database, including 36,136 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 0.27 (6733 hom., cov: 31)
  • Exomes 𝑓: 0.26 (29403 hom.)
• Consequence: UBQLN4 NM_020131.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• Publications: 6 publications found

Genes affected

UBQLN4 (HGNC:1237): (ubiquilin 4) Enables K48-linked polyubiquitin modification-dependent protein binding activity and identical protein binding activity. Involved in cellular response to DNA damage stimulus; negative regulation of double-strand break repair via homologous recombination; and regulation of cellular catabolic process. Located in several cellular components, including autophagosome; nucleoplasm; and site of DNA damage. Part of protein-containing complex. Colocalizes with cytosolic proteasome complex and nuclear proteasome complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020131.5. 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
	UBQLN4	NM_020131.5	MANE Select	c.*756A>G		3_prime_UTR	Exon 11 of 11	NP_064516.2
	UBQLN4	NM_001304342.2		c.*756A>G		3_prime_UTR	Exon 11 of 11	NP_001291271.1	B4DZF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN4	ENST00000368309.4	TSL:1 MANE Select	c.*756A>G		3_prime_UTR	Exon 11 of 11	ENSP00000357292.3	Q9NRR5-1
	UBQLN4	ENST00000879792.1		c.*756A>G		3_prime_UTR	Exon 11 of 11	ENSP00000549851.1
	UBQLN4	ENST00000932515.1		c.*756A>G		3_prime_UTR	Exon 11 of 11	ENSP00000602574.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40909 AN: 151990 Hom.: 6726 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.263 AC: 218902 AN: 833270 Hom.: 29403 Cov.: 32 AF XY: 0.262 AC XY: 100705 AN XY: 384806

African (AFR) AF: 0.182 AC: 2876 AN: 15786

American (AMR) AF: 0.367 AC: 361 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 1114 AN: 5152

East Asian (EAS) AF: 0.818 AC: 3082 AN: 3768

South Asian (SAS) AF: 0.289 AC: 4759 AN: 16460

European-Finnish (FIN) AF: 0.318 AC: 89 AN: 280

Middle Eastern (MID) AF: 0.185 AC: 300 AN: 1620

European-Non Finnish (NFE) AF: 0.261 AC: 198504 AN: 761920

Other (OTH) AF: 0.286 AC: 7817 AN: 27300

GnomAD4 genome AF: 0.269 AC: 40934 AN: 152108 Hom.: 6733 Cov.: 31 AF XY: 0.276 AC XY: 20508 AN XY: 74350

African (AFR) AF: 0.188 AC: 7785 AN: 41514

American (AMR) AF: 0.331 AC: 5052 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 706 AN: 3466

East Asian (EAS) AF: 0.835 AC: 4328 AN: 5184

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3124 AN: 10580

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17730 AN: 67978

Other (OTH) AF: 0.272 AC: 574 AN: 2108

Alfa AF: 0.255 Hom.: 673

Bravo AF: 0.275

Asia WGS AF: 0.515 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.5
DANN	Benign	0.69
PhyloP100		0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

Other links and lift over

dbSNP: rs3820592; hg19: chr1-156006013;