chr17-16382492-C-T

Variant names:

• chr17-16382492-C-T
• rs149612063
• NM_018955.4:c.585C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018955.4(UBB):​c.585C>T​(p.Leu195Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,613,170 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: UBB NM_018955.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.29
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-16382492-C-T is Benign according to our data. Variant chr17-16382492-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 728462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.29 with no splicing effect.
• BS2: High AC in GnomAd4 at 274 AD gene.

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.585C>T	p.Leu195Leu	synonymous	Exon 2 of 2	NP_061828.1	P0CG47
	UBB	NM_001281716.2		c.585C>T	p.Leu195Leu	synonymous	Exon 2 of 2	NP_001268645.1	Q5U5U6
	UBB	NM_001281717.1		c.585C>T	p.Leu195Leu	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.585C>T	p.Leu195Leu	synonymous	Exon 2 of 2	ENSP00000304697.3	P0CG47
	UBB	ENST00000395837.1	TSL:2	c.585C>T	p.Leu195Leu	synonymous	Exon 2 of 2	ENSP00000379178.1	P0CG47
	UBB	ENST00000395839.5	TSL:2	c.585C>T	p.Leu195Leu	synonymous	Exon 2 of 2	ENSP00000379180.1	P0CG47

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 274 AN: 151632 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00209

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00153 AC: 385 AN: 251024 AF XY: 0.00150

Gnomad AFR exome AF: 0.000432

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.00249

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00247 AC: 3614 AN: 1461420 Hom.: 9 Cov.: 31 AF XY: 0.00239 AC XY: 1741 AN XY: 727014

African (AFR) AF: 0.000388 AC: 13 AN: 33466

American (AMR) AF: 0.00132 AC: 59 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

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

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86232

European-Finnish (FIN) AF: 0.00189 AC: 101 AN: 53420

Middle Eastern (MID) AF: 0.000359 AC: 2 AN: 5568

European-Non Finnish (NFE) AF: 0.00294 AC: 3266 AN: 1111840

Other (OTH) AF: 0.00219 AC: 132 AN: 60346

GnomAD4 genome AF: 0.00181 AC: 274 AN: 151750 Hom.: 0 Cov.: 32 AF XY: 0.00165 AC XY: 122 AN XY: 74140

African (AFR) AF: 0.000774 AC: 32 AN: 41334

American (AMR) AF: 0.00112 AC: 17 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4786

European-Finnish (FIN) AF: 0.00209 AC: 22 AN: 10530

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

European-Non Finnish (NFE) AF: 0.00293 AC: 199 AN: 67946

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.00244 Hom.: 0

EpiCase AF: 0.00267

EpiControl AF: 0.00249

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		2.3
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149612063; hg19: chr17-16285806;