4-39722543-A-G

Variant names:

• chr4-39722543-A-G
• rs461962
• NM_005339.5:c.64-14877A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005339.5(UBE2K):​c.64-14877A>G variant causes a intron 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UBE2K NM_005339.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 1 publications found

Genes affected

UBE2K (HGNC:4914): (ubiquitin conjugating enzyme E2 K) The protein encoded by this gene belongs to the ubiquitin-conjugating enzyme family. This protein interacts with RING finger proteins, and it can ubiquitinate huntingtin, the gene product for Huntington's disease. Known functions for this protein include a role in aggregate formation of expanded polyglutamine proteins and the suppression of apoptosis in polyglutamine diseases, a role in the dislocation of newly synthesized MHC class I heavy chains from the endoplasmic reticulum, and involvement in foam cell formation. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005339.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2K	NM_005339.5	MANE Select	c.64-14877A>G		intron	N/A	NP_005330.1
	UBE2K	NM_001111112.2		c.64-14877A>G		intron	N/A	NP_001104582.1
	UBE2K	NM_001111113.2		c.63+24153A>G		intron	N/A	NP_001104583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2K	ENST00000261427.10	TSL:1 MANE Select	c.64-14877A>G		intron	N/A	ENSP00000261427.5
	UBE2K	ENST00000445950.2	TSL:1	c.64-14877A>G		intron	N/A	ENSP00000390483.2
	UBE2K	ENST00000503368.5	TSL:1	c.63+24153A>G		intron	N/A	ENSP00000421203.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-1.7

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: rs461962; hg19: chr4-39724163;