rs551835

Variant names:

• chr18-160887-A-G
• rs551835
• NM_005151.4:c.16+2173A>G

Variant summary

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

The NM_005151.4(USP14):​c.16+2173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,150 control chromosomes in the GnomAD database, including 2,549 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 0.17 (2549 hom., cov: 33)
• Consequence: USP14 NM_005151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 3 publications found

Genes affected

USP14 (HGNC:12612): (ubiquitin specific peptidase 14) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mice with a mutation that results in reduced expression of the ortholog of this protein are retarded for growth, develop severe tremors by 2 to 3 weeks of age followed by hindlimb paralysis and death by 6 to 10 weeks of age. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

USP14 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005151.4. 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
	USP14	NM_005151.4	MANE Select	c.16+2173A>G		intron	N/A	NP_005142.1	P54578-1
	USP14	NM_001037334.2		c.16+2173A>G		intron	N/A	NP_001032411.1	P54578-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP14	ENST00000261601.8	TSL:1 MANE Select	c.16+2173A>G		intron	N/A	ENSP00000261601.6	P54578-1
	USP14	ENST00000947712.1		c.16+2173A>G		intron	N/A	ENSP00000617771.1
	USP14	ENST00000873770.1		c.16+2173A>G		intron	N/A	ENSP00000543829.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26588 AN: 152032 Hom.: 2545 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.175 AC: 26614 AN: 152150 Hom.: 2549 Cov.: 33 AF XY: 0.171 AC XY: 12697 AN XY: 74400

African (AFR) AF: 0.119 AC: 4928 AN: 41506

American (AMR) AF: 0.148 AC: 2260 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3472

East Asian (EAS) AF: 0.00753 AC: 39 AN: 5182

South Asian (SAS) AF: 0.200 AC: 963 AN: 4820

European-Finnish (FIN) AF: 0.170 AC: 1798 AN: 10590

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15428 AN: 67994

Other (OTH) AF: 0.161 AC: 339 AN: 2110

Alfa AF: 0.203 Hom.: 4322

Bravo AF: 0.167

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.68
PhyloP100		-0.52
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: rs551835; hg19: chr18-160887;