17-16382006-G-A

Variant names:

• chr17-16382006-G-A
• rs397839871
• NM_018955.4:c.99G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_018955.4(UBB):​c.99G>A​(p.Lys33Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBB NM_018955.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270
• Publications: 2 publications found

Genes affected

UBB (HGNC:12463): (ubiquitin B) This gene encodes ubiquitin, one of the most conserved proteins known. Ubiquitin has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene consists of three direct repeats of the ubiquitin coding sequence with no spacer sequence. Consequently, the protein is expressed as a polyubiquitin precursor with a final amino acid after the last repeat. An aberrant form of this protein has been detected in patients with Alzheimer's disease and Down syndrome. Pseudogenes of this gene are located on chromosomes 1, 2, 13, and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

UBB Gene-Disease associations (from GenCC):

• isolated cleft palate

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000265401 (HGNC:58390):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 17-16382006-G-A is Benign according to our data. Variant chr17-16382006-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 718573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.027 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018955.4. 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
	UBB	NM_018955.4	MANE Select	c.99G>A	p.Lys33Lys	synonymous	Exon 2 of 2	NP_061828.1	P0CG47
	UBB	NM_001281716.2		c.99G>A	p.Lys33Lys	synonymous	Exon 2 of 2	NP_001268645.1	Q5U5U6
	UBB	NM_001281717.1		c.99G>A	p.Lys33Lys	synonymous	Exon 2 of 2	NP_001268646.1	P0CG47

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBB	ENST00000302182.8	TSL:1 MANE Select	c.99G>A	p.Lys33Lys	synonymous	Exon 2 of 2	ENSP00000304697.3	P0CG47
	UBB	ENST00000395837.1	TSL:2	c.99G>A	p.Lys33Lys	synonymous	Exon 2 of 2	ENSP00000379178.1	P0CG47
	UBB	ENST00000395839.5	TSL:2	c.99G>A	p.Lys33Lys	synonymous	Exon 2 of 2	ENSP00000379180.1	P0CG47

Frequencies

GnomAD3 genomes AF: 0.00249 AC: 307 AN: 123344 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00320

Gnomad AMI AF: 0.00729

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.00525

Gnomad FIN AF: 0.00447

Gnomad MID AF: 0.0149

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.00468

GnomAD2 exomes AF: 0.00000422 AC: 1 AN: 236778 AF XY: 0.00000778

Gnomad AFR exome AF: 0.0000667

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000182 AC: 26 AN: 1426380 Hom.: 0 Cov.: 31 AF XY: 0.0000225 AC XY: 16 AN XY: 709738

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000939 AC: 3 AN: 31944

American (AMR) AF: 0.0000235 AC: 1 AN: 42480

Ashkenazi Jewish (ASJ) AF: 0.0000811 AC: 2 AN: 24648

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37444

South Asian (SAS) AF: 0.00 AC: 0 AN: 84556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.0000165 AC: 18 AN: 1089624

Other (OTH) AF: 0.0000173 AC: 1 AN: 57906

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00250 AC: 308 AN: 123440 Hom.: 0 Cov.: 31 AF XY: 0.00230 AC XY: 140 AN XY: 60950

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00319 AC: 104 AN: 32596

American (AMR) AF: 0.00183 AC: 23 AN: 12602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2936

East Asian (EAS) AF: 0.00483 AC: 19 AN: 3934

South Asian (SAS) AF: 0.00526 AC: 19 AN: 3614

European-Finnish (FIN) AF: 0.00447 AC: 38 AN: 8496

Middle Eastern (MID) AF: 0.0158 AC: 3 AN: 190

European-Non Finnish (NFE) AF: 0.00155 AC: 88 AN: 56656

Other (OTH) AF: 0.00520 AC: 9 AN: 1730

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0114 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.88
DANN	Benign	0.73
PhyloP100		-0.027
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=96/4	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: rs397839871; hg19: chr17-16285320; COSMIC: COSV56219171; COSMIC: COSV56219171;