16-4874333-C-G

Variant names:

• chr16-4874333-C-G
• NM_001079514.3:c.1923C>G
• UBN1 p.Leu641Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001079514.3(UBN1):​c.1923C>G​(p.Leu641Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L641L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBN1 NM_001079514.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 0 publications found

Genes affected

UBN1 (HGNC:12506): (ubinuclein 1) Cellular senescence is a hallmark of tumor suppression and tissue aging. Senescent cells contain domains of heterochromatin, called senescence-associated heterochromatin foci (SAHF), that repress proliferation-promoting genes. The protein encoded by this gene binds to proliferation-promoting genes and is required for SAHF formation, enhancing methylation of histone H3. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.651 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079514.3. 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
	UBN1	NM_001079514.3	MANE Select	c.1923C>G	p.Leu641Leu	synonymous	Exon 15 of 18	NP_001072982.1	Q9NPG3-1
	UBN1	NM_001288656.1		c.1923C>G	p.Leu641Leu	synonymous	Exon 15 of 17	NP_001275585.1	Q9NPG3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBN1	ENST00000262376.11	TSL:1 MANE Select	c.1923C>G	p.Leu641Leu	synonymous	Exon 15 of 18	ENSP00000262376.5	Q9NPG3-1
	UBN1	ENST00000396658.8	TSL:1	c.1923C>G	p.Leu641Leu	synonymous	Exon 14 of 17	ENSP00000379894.3	Q9NPG3-1
	UBN1	ENST00000931634.1		c.1896C>G	p.Leu632Leu	synonymous	Exon 15 of 18	ENSP00000601693.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.7
DANN	Benign	0.67
PhyloP100		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-4924334;