15-74452342-C-A

Variant names:

• chr15-74452342-C-A
• rs749570682
• NM_032907.5:c.341G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032907.5(UBL7):​c.341G>T​(p.Arg114Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,409,424 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R114P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: UBL7 NM_032907.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05
• Publications: 0 publications found

Genes affected

UBL7 (HGNC:28221): (ubiquitin like 7) Predicted to enable polyubiquitin modification-dependent protein binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032907.5. 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
	UBL7	NM_032907.5	MANE Select	c.341G>T	p.Arg114Leu	missense	Exon 4 of 11	NP_116296.1	Q96S82
	UBL7	NM_001286741.2		c.461G>T	p.Arg154Leu	missense	Exon 4 of 11	NP_001273670.1
	UBL7	NM_001286742.2		c.461G>T	p.Arg154Leu	missense	Exon 5 of 12	NP_001273671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL7	ENST00000395081.7	TSL:1 MANE Select	c.341G>T	p.Arg114Leu	missense	Exon 4 of 11	ENSP00000378518.2	Q96S82
	UBL7	ENST00000564488.5	TSL:1	c.341G>T	p.Arg114Leu	missense	Exon 5 of 12	ENSP00000454828.1	Q96S82
	UBL7	ENST00000565335.5	TSL:1	c.341G>T	p.Arg114Leu	missense	Exon 5 of 12	ENSP00000457708.1	Q96S82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1409424 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 696036

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

African (AFR) AF: 0.00 AC: 0 AN: 32430

American (AMR) AF: 0.0000270 AC: 1 AN: 37090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25258

East Asian (EAS) AF: 0.00 AC: 0 AN: 37124

South Asian (SAS) AF: 0.00 AC: 0 AN: 80098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083754

Other (OTH) AF: 0.00 AC: 0 AN: 58344

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.24
Sift	Benign	0.28	T
Sift4G	Benign	0.16	T
Polyphen		0.91	P
Vest4		0.69
MutPred		0.58		Loss of MoRF binding (P = 0.0198)
MVP		0.61
MPC		0.38
ClinPred		0.80	D
GERP RS		5.5
PromoterAI		-0.051	Neutral
Varity_R		0.20
gMVP		0.71

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: rs749570682; hg19: chr15-74744683; COSMIC: COSV63706264; COSMIC: COSV63706264;